Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  74 LGSSASLDCGFSMAPGLDLISVEWRLQHKGRGQ--LVYSWTAGQGQAVRKGATlEPAQLGMARDASLTLPGLTIQDEGTY 151
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPtfLIAYYSNGSEEGVKKGRF-SGRGDPSNGDGSLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|
gi 1189690202 152 ICQITTSLY-RAQQIIQLNI 170
Cdd:pfam07686  89 TCAVIPSGEgVFGKGTRLTV 108

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1189690202  188 TLICDIAGYYPLDVVVTWTReelGGSPAQvSGASFSSLRQSVAGTYSISSSLT--AEPGSAGATYTCQVTHISLEEP 262
Cdd:smart00407   3 TLVCLVSGFYPPDITVTWLR---NGQEVT-EGVSTTDPLKNSDGTYFLSSYLTvpASTWESGDVYTCQVTHEGLKEP 75

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  74 LGSSASLDCGFSMAPGLDLISVEWRLQHKGRGQ--LVYSWTAGQGQAVRKGATlEPAQLGMARDASLTLPGLTIQDEGTY 151
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPtfLIAYYSNGSEEGVKKGRF-SGRGDPSNGDGSLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|
gi 1189690202 152 ICQITTSLY-RAQQIIQLNI 170
Cdd:pfam07686  89 TCAVIPSGEgVFGKGTRLTV 108

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202   68 QSLSFLLGSSASLDCGFSmapGLDLISVEWR------LQHKGRGQLVYSwtagqgqavrkgatlepaqlgmARDASLTLP 141
Cdd:smart00410   2 PSVTVKEGESVTLSCEAS---GSPPPEVTWYkqggklLAESGRFSVSRS----------------------GSTSTLTIS 56

                           90       100
                   ....*....|....*....|....*....
gi 1189690202  142 GLTIQDEGTYICQITTSLYRAQQIIQLNI 170
Cdd:smart00410  57 NVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 173 SPKVRLSLANEAllpTLICDIAGYYPLDVVVTWTReelGGSPAQVSGASFSSLRQSvAGTYSISSSLTAEPGS--AGATY 250
Cdd:cd00098     6 PPSPEEKGGGKV---TLVCLVSGFYPKDITVTWLK---NGVPLTSGVSTSSPVEPN-DGTYSVTSSLTVPPSDwdEGATY 78

                          90
                  ....*....|...
gi 1189690202 251 TCQVTHISLEEPL 263
Cdd:cd00098    79 TCVVTHESLKSPL 91

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 173 SPKVRLSlANEALLP---TLICDIAGYYPLDVVVTWTReelGGSPaQVSGASFSSLRQSVAGTYSISSSLTAEPGSaGAT 249
Cdd:cd21029     2 KPRVRLS-SRPSPGDghlQLSCHVTGFYPRPIEVTWLR---DGQE-QMDGTQSGGILPNHDGTYQLRKTLDIAPGE-GAG 75

                          90
                  ....*....|....
gi 1189690202 250 YTCQVTHISLEEPL 263
Cdd:cd21029    76 YSCRVDHSSLKQDL 89

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 174 PKVRLSLANEALL---PTLICDIAGYYPLDVVVTWTREelggSPAQVSGASFSSLRQSVAGTYSISSSLTAEPgSAGATY 250
Cdd:cd05766     4 PSVKVSPTKTGPLehpNLLVCSVTGFYPAEIEVKWFRN----GQEETAGVVSTELIPNGDWTFQILVMLETTP-RRGDVY 78

                          90
                  ....*....|...
gi 1189690202 251 TCQVTHISLEEPL 263
Cdd:cd05766    79 TCQVEHSSLQSPL 91

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 188 TLICDIAGYYPLDVVVTWtreELGGSPAQvSGASFSSLRQSVAGTYSISS--SLTAEPGSAGATYTCQVTHISLEEPLGA 265
Cdd:cd07699    20 TLVCLINKFYPGFATVTW---KVDGSTVS-SGVTTSKTEQQSDNTYSMSSylTLSSSDWNKHKVYTCEVTHEGLSSTITK 95

                  .
gi 1189690202 266 S 266
Cdd:cd07699    96 S 96

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin E (IgE); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second constant domain of the heavy chain of immunoglobulin E (IgE). The basic structure of immunoglobulin (Ig) molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta, and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). The different classes of antibodies vary in their heavy chains; the IgE class has the epsilon type. This domain (Cepsilon2) of IgE is in place of the flexible hinge region found in IgG.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 189 LICDIAGYYPLDVVVTWTreeLGGSPAQVSGASFSSLRQSvAGTYSISS--SLTAEPGSAGATYTCQVTH 256
Cdd:cd05847    21 LLCLISGYTPSTIEVEWL---VDGQVATLSAASTAPQKEE-GGTFSTTSklNVTQEDWKSGKTYTCKVTH 86

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  74 LGSSASLDCGFSMAPGLDLISVEWRLQHKGRGQ--LVYSWTAGQGQAVRKGATlEPAQLGMARDASLTLPGLTIQDEGTY 151
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPtfLIAYYSNGSEEGVKKGRF-SGRGDPSNGDGSLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|
gi 1189690202 152 ICQITTSLY-RAQQIIQLNI 170
Cdd:pfam07686  89 TCAVIPSGEgVFGKGTRLTV 108

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  59 VEFQVMTQTQSLsflLGSSASLDCGF-SMAPGLDLISVEWrlQHKGRGQLVYSWTAGQGQAVRKGATLE--PAQLGMA-R 134
Cdd:cd20989     1 VRVQVPPEVRGF---LGGSVTLPCHLlPPNMVTHVSQVTW--QRHDEHGSVAVFHPKQGPSFPESERLSfvAARLGAElR 75

                          90       100
                  ....*....|....*....|...
gi 1189690202 135 DASLTLPGLTIQDEGTYICQITT 157
Cdd:cd20989    76 NASLAMFGLRVEDEGNYTCEFAT 98

Immunoglobulin variable (IgV) domain of B7-H6; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H6 (also known as NCR3LG1). B7-H6 contains one IgV domain and one IgC domain (IgV-IgC) and belongs to the B7-family, which consists of structurally related cell-surface protein ligands which bind to receptors on lymphocytes that regulate immune responses. B7-H6 is a ligand of NKp30, which is a member of CD28 family and an activating receptor of natural killer (NK) cells. The expression of NKp30 has been found in most of NK cells, which is involved in the process of tumor cell killing and interaction with antigen presenting cells (APCs) such as dendritic cells. Studies showed that NK cells eliminate B7-H6-expressing tumor cells either directly via cytotoxicity or indirectly by cytokine secretion. For instance, chimeric NKp30-expressing T cells responded to B7-H6(+) tumor cells and those T cells produced IFN-gamma and killed B7-H6-expressing tumor cells in vivo. B7-H6 mRNA is not found in normal cells, while high expression of B7-H6 is found in certain type tumor cells, such as lymphoma, leukemia, ovarian cancer, brain tumors, breast cancers, and various sarcomas. Since B7-H6 can bind NKp30 to exert anti-tumor effects by NK cells, which are able to recognize the difference between cancer cells and normal cells, B7-H6 may serve as a promising target for cancer immunotherapy.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1189690202 108 VYSWTAGQGQAVRKGATLEPAQLGMArDASLTLPGLTIQDEGTYICQITTSLYRAQQIIQLNI 170
Cdd:cd20981    53 VFEFFGDHQKAFRPGAIVSPWRLKSG-DASLQLPGVQLEEAGEYRCEVVVTPLKAQGTVQLEV 114

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  64 MTQT-QSLSFLLGSSASLDCGFSMAPGLDLISveWRLQHKGRG-QLVYSWTAGQGQAVRKGATLEPAQLGMARDASLTLP 141
Cdd:cd00099     1 VTQSpRSLSVQEGESVTLSCEVSSSFSSTYIY--WYRQKPGQGpEFLIYLSSSKGKTKGGVPGRFSGSRDGTSSFSLTIS 78

                          90
                  ....*....|....*..
gi 1189690202 142 GLTIQDEGTYICQITTS 158
Cdd:cd00099    79 NLQPEDSGTYYCAVSES 95

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1189690202 188 TLICDIAGYYPLDVVVTWTREelgGSPAQ--VSGASFSSLRQsvaGTYSISSSLTAEPgSAGATYTCQVTHISLEEPL 263
Cdd:cd05767    20 TLICFVDNFFPPVINVTWLRN---GQPVTdgVSETVFLPRED---HSFRKFSYLPFTP-SEGDIYDCRVEHWGLEEPL 90

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of human histocompatibility antigen (HLA) DQ and mouse I-A. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes; these peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC, and bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 171 QASPKVRLSLA-NEAL--LPTLICDIAGYYPLDVVVTWTREELggspAQVSGASFSSLRQSVAGTYSISSSLTAEPgSAG 247
Cdd:cd21001     1 RVEPTVTISPSrTEALnhHNLLVCSVTDFYPGQIKVRWFRNDQ----EETAGVVSTPLIRNGDWTFQILVMLEMTP-QRG 75

                          90
                  ....*....|....*.
gi 1189690202 248 ATYTCQVTHISLEEPL 263
Cdd:cd21001    76 DVYTCHVEHPSLQSPI 91

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G. HLA-G histocompatibility antigen (also known as human leukocyte antigen G ; HLA-G) is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogs. This class I molecule is a heterodimer consisting of a heavy chain and light chain, beta-2-microglobulin. The heavy chain is anchored in the membrane. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I and class II. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. MHC class II molecules play a key role in the initiation of the antigen-specific immune repose. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1189690202 188 TLICDIAGYYPLDVVVTWTREelggSPAQVSGASFSSLRQSVAGTYSISSSLTAePGSAGATYTCQVTHISLEEPL 263
Cdd:cd21022    20 TLRCWALGFYPAEIILTWQRD----GEDQTQDVELVETRPAGDGTFQKWAAVVV-PSGEEQRYTCHVQHEGLPEPL 90

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  75 GSSASLDCGF-SMAPGLDLISVEWRLQ--HKGRGQLV-------YSWTAG--QGQAVRKGATlepaqlgMARDASLTLPG 142
Cdd:cd05880    14 GTDVRLKCTFsSSAPIGDTLVITWNFRplDGGREESVfyyhkrpYPPPDGrfKGRVVWDGNI-------MRRDASILIWQ 86

                          90
                  ....*....|...
gi 1189690202 143 LTIQDEGTYICQI 155
Cdd:cd05880    87 LQPTDNGTYTCQV 99

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  75 GSSASLDCGF-SMAPGLDLISVEWRLQHKGRGQLVYSWTAGQGQAVrkgaTLEPAQLG---------MARDASLTLPGLT 144
Cdd:cd05715    14 GSDVRLTCTFtSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKPY----ILKVGRFKdrvswagnpSKKDASIVISNLQ 89

                          90
                  ....*....|.
gi 1189690202 145 IQDEGTYICQI 155
Cdd:cd05715    90 FSDNGTYTCDV 100

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  75 GSSASLDCGFSMAPG----LDlisVEWRLQ---HKGRGQLVYSwtagqgqAVRKGATLEPAQLG--------MARDASLT 139
Cdd:cd20960    15 GENVTLPCHHQLGLEdqgtLD---IEWLLLpsdKVEKVVITYS-------GDRVYNHYYPALKGrvaftsndLSGDASLN 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 1189690202 140 LPGLTIQDEGTYICQITTSLYRAQQIIQLN 169
Cdd:cd20960    85 ISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

CH3 domain (third constant Ig domain of heavy chains) in immunoglobulin heavy alpha, epsilon, and mu chains, and CH2 domain (second constant Ig domain of the gheavy chain) in immunoglobulin heavy gamma chain; member of the C1-set of Ig superfamily (IgSF) ; The members here are composed of the third immunoglobulin constant domain (IgC) of the gamma heavy chains and the second immunoglobulin constant domain (IgC) of alpha, epsilon, and mu heavy chains. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 170 IQASPKvRLSLANEALLPTLICDIAGYYplDVVVTWTREElgGSPAQvsgASFSSLRQSVAGTYSISSSLTAEPGS--AG 247
Cdd:cd07696     6 IPPSPK-DLFLTKSAKVTCLVVDLTSIE--EVNVTWSRED--GNEVL---ASTTNPEKHYNATLSVVSTLTVCADDwdNG 77

                          90       100
                  ....*....|....*....|.
gi 1189690202 248 ATYTCQVTHISLEEPLGASTQ 268
Cdd:cd07696    78 KTFKCKVTHPDLPSPIVKSIQ 98

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of T10, T22, and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of the murine H-2T-encoded T10, T22, and similar proteins. T10 and T22 are highly related nonclassical major histocompatibility complex (MHC) class Ib proteins that bind to certain gammadelta T cell receptors (TCRs) in the absence of other components. Classical MHC class I (class Ia) molecules participate in immune responses by presenting peptide antigens to cytolytic alpha beta T cells. Many nonclassical MHC class I (class Ib) molecules have distinct antigen-binding capabilities, suggesting that they have evolved for specific tasks that are distinct from those of MHC class Ia. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1189690202 188 TLICDIAGYYPLDVVVTWTR--EELggspaqVSGASFSSLRQSVAGTYSISSSLTAEPGSAgATYTCQVTHISLEEPL 263
Cdd:cd21016    21 TLRCWALGFYPADITLTWQKdgEEL------TQDMEFVETRPAGDGTFQKWAAVVVPLGKE-QSYTCHVYHEGLPEPL 91

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP. HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DP is an alphabeta heterodimer cell-surface receptor. Each DP subunit (alpha-subunit, beta-subunit) is composed of a alpha-helical N-terminal domain, an IgG-like beta sheet, a membrane spanning domain, and a cytoplasmic domain. The alpha-helical domain forms the sides of the peptide binding groove. The beta sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 174 PKVRLSLANEALLP---TLICDIAGYYPLDVVVTWTREelggSPAQVSGASFSSLRQSVAGTYSISSSLTAEPgSAGATY 250
Cdd:cd21003     4 PKVNVSPSKKGPLQhhnLLVCHVTDFYPGNIQVRWFLN----GQEETAGVVSTNLIHNGDWTFQILVMLEMTP-QQGDVY 78

                          90
                  ....*....|...
gi 1189690202 251 TCQVTHISLEEPL 263
Cdd:cd21003    79 TCQVEHPSLDSPV 91

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin heavy alpha chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant-1 set domain (IgC) of alpha heavy chains. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202 177 RLSL---ANEALL----PTLICDIAGYY-PLDVVVTWTreelggsPAQVSGASFSSLRQSVAGTYSISSSL--TAEPGSA 246
Cdd:cd04986     3 RLSLqrpALEDLLlgsnASLTCTLSGLKdPEGATFTWE-------PSGGKEAIQGPPERDSCGCYSVSSVLpgCAEPWNS 75

                          90       100
                  ....*....|....*....|
gi 1189690202 247 GATYTCQVTHISLEEPLGAS 266
Cdd:cd04986    76 GDTFSCTVTHPESKGTLTAT 95

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H-2Kb; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H-2Kb. H-2Kb is an alloantigen for the 2C T cell receptor (TCR). H-2Kb forms a complex with beta-2-microglobulin, and a peptide, including VSV-8 (RGYVYNGL), SEV-9 (FAPGNYPAL), and OVA-8 (SIINFEKL). Comparison of the OVA-8, VSV-8, and SEV-9 complexes with H-2Kb indicates that four side chains (Lys-66, Glu-152, Arg-155, and Trp-167) adopt peptide-specific conformations. H-2Kb paralogs include H-2Db, H-2Kbml and H-2KbI1s. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1189690202 188 TLICDIAGYYPLDVVVTWtreELGGSPAqVSGASFSSLRQSVAGTYSISSSLTAePGSAGATYTCQVTHISLEEPL 263
Cdd:cd21019    20 TLRCWALGFYPADITLTW---QLNGEEL-IQDMELVETRPAGDGTFQKWASVVV-PLGKEQYYTCHVYHQGLPEPL 90

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld. H-2Ld complexed with peptide QL9 (or p2Ca) and complexed with influenza virus peptide NP366-374 (ASNEN-METM), respectively are high-affinity alloantigens for the 2C T cell receptor (TCR). The a1-a2 super domains of H-2Ld, H-2Db, and H-2Kb closely superimpose. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1189690202 188 TLICDIAGYYPLDVVVTWtreELGGSPAqVSGASFSSLRQSVAGTYSISSSLTAePGSAGATYTCQVTHISLEEPL 263
Cdd:cd21018    21 TLRCWALGFYPADITLTW---QLNGEEL-TQDMELVETRPAGDGTFQKWASVVV-PLGKEQNYTCRVYHEGLPEPL 91

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of QA-2. Qa-2 is a nonclassical MHC Ib antigen, which has been implicated in both innate and adaptive immune responses, as well as embryonic development. Qa-2 has an unusual peptide binding specificity in that it requires two dominant C-terminal anchor residues and is capable of associating with a substantially more diverse array of peptide sequences than other nonclassical MHC. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1189690202 188 TLICDIAGYYPLDVVVTWtreELGGSPAqVSGASFSSLRQSVAGTYSISSSLTAePGSAGATYTCQVTHISLEEPL 263
Cdd:cd21014    20 TLRCWALGFYPADITLTW---QLNGEEL-TQDMELVETRPAGDGTFQKWASVVV-PLGKEQNYTCHVNHEGLPEPL 90

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of HLA-Cw3 and HLA-Cw4; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of HLA-Cw3 and HLA-Cw4. HLA-C belongs to the MHC class I heavy chain receptors. The C receptor is a heterodimer consisting of a HLA-C mature gene product and beta-2-microglobulin. The mature C chain is anchored in the membrane. MHC Class I molecules, like HLA-C, are expressed in nearly all cells, and present small peptides to the immune system which surveys for non-self peptides. HLA-C is a locus on chromosome 6, which encodes for a large number of HLA-C alleles that are Class-I MHC receptors. Class Ib histocompatibility leukocyte antigens (HLA)-Cw3 and (HLA)-Cw4 are ligands for the natural killer (NK) cell inhibitory receptors KIR2DL2 and KIR2DL1, respectively. HLA-Cw3 and related alleles (HLA-Cw1, -Cw7, and -Cw8) contain Ser77 and Asn80 and interact with KIR that are reactive with the GL183 antibody Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. HLA-Cw4 and related alleles (HLA-Cw2, -Cw5, and -Cw6) have Asn77 and Lys80 and are recognized by KIR reactive with the EB6 15 or HP-3E4 16 antibody. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1189690202 188 TLICDIAGYYPLDVVVTWTREelggSPAQVSGASFSSLRQSVAGTYSISSSLTAePGSAGATYTCQVTHISLEEPL 263
Cdd:cd21025    21 TLRCWALGFYPAEITLTWQWD----GEDQTQDTELVETRPAGDGTFQKWAAVVV-PSGEEQRYTCHVQHEGLPEPL 91

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1189690202 191 CDIAGYYPLDVVVTWTREELGGS-----PAQVSGasfsslrqsvaGTYSISSSLT--AEPGSAGATYTCQVTH 256
Cdd:cd21818    22 CLVQGFFPEPVNVTWNYSGKGGTarnfpAMLASG-----------GRYTQSSQLTlpADQCPEGEAYKCSVQH 83

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1189690202  75 GSSASLDCGFSMAPGLDLIS--VEWRLQHKGRGQLVYSWT--AGQGQAVRKGATLEPAQLGMARdASLTLPGLTIQDEGT 150
Cdd:cd20947    13 GSNMTIECKFPVEKQLDLAAliVYWEMEDKNIIQFVHGEEdlKVQHSSYRQRARLLKDQLSLGN-AALQITDVKLQDAGV 91

                  ....*.
gi 1189690202 151 YICQIT 156
Cdd:cd20947    92 YRCMIS 97