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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      112 APSVFIFPPSEDQVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSkDNTYSLSSTLTLSSTEYQSHKV 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
8TOP_Z      192 YACEVTHQGLSSPVTKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      112 APSVFIFPPSEDQVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSkDNTYSLSSTLTLSSTEYQSHKV 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
8TOP_Z      192 YACEVTHQGLSSPVTKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
8TOP_Z         129 TVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSkDNTYSLSSTLTLSSTEYQSHKVYACEVTHQGLSSP 204
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNS-DGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKEP 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z          6 QSPSSLSASVGDRVTITCRASQDISS---FLNWYQQKPGKAPKLLI--SSVNRLESGVPSRFSGSG--SGTEFTLTVSSL 78
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEastSVYWYRQPPGKGPTFLIayYSNGSEEGVKKGRFSGRGdpSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
8TOP_Z         79 QPEDFATYSCQQCGSVPYTFGQGTTLEI 106
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      112 APSVFIFPPSEDQVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSkDNTYSLSSTLTLSSTEYQSHKV 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
8TOP_Z      192 YACEVTHQGLSSPVTKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z        4 MTQSPSSLSASVGDRVTITCRASQDISS-FLNWYQQKPGKAPKLLI---SSVNRLESGVPSRFSGSGSG-TEFTLTVSSL 78
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSStYIYWYRQKPGQGPEFLIylsSSKGKTKGGVPGRFSGSRDGtSSFSLTISNL 80

                        90       100       110
                ....*....|....*....|....*....|.
8TOP_Z       79 QPEDFATYSCQQ---CGSVPYTFGQGTTLEI 106
Cdd:cd00099  81 QPEDSGTYYCAVsesGGTDKLTFGSGTRLTV 111

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z        5 TQSPSSLSASVGDRVTITCRASQDISSFLNWYQQKPGKAPKLLI---SSVNRLESGvpsRFSGSGSGTE--FTLTVSSLQ 79
Cdd:cd04983   2 TQSPQSLSVQEGENVTLNCNYSTSTFYYLFWYRQYPGQGPQFLIyisSDSGNKKKG---RFSATLDKSRksSSLHISAAQ 78

                        90       100       110
                ....*....|....*....|....*....|.
8TOP_Z       80 PEDFATYSCQQCGSVPY---TFGQGTTLEIK 107
Cdd:cd04983  79 LSDSAVYFCALSESGGTgklTFGKGTRLTVE 109

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      114 SVFIFPPSEDQVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESvTEQDSKDNTYSLSSTLTLSSTEYQSHKVYA 193
Cdd:cd00098   1 TVTLLPPSPEEKGGGKVTLVCLVSGFYPKDITVTWLKNGVPLTSGVSTS-SPVEPNDGTYSVTSSLTVPPSDWDEGATYT 79

                        90
                ....*....|....*.
8TOP_Z      194 CEVTHQGLSSPVTKSF 209
Cdd:cd00098  80 CVVTHESLKSPLSKTW 95

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z          19 VTITCRASQD--ISSFLNWYQQKPGKAPKLLIS----SVNRLESGVPSRFSGSG--SGTEFTLTVSSLQPEDFATYSCQQ 90
Cdd:smart00406   2 VTLSCKFSGStfSSYYVSWVRQPPGKGLEWLGYigsnGSSYYQESYKGRFTISKdtSKNDVSLTISNLRVEDTGTYYCAV 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z           8 PSSLSASVGDRVTITCRASQDISSFLNWYQQKPgkapKLLISsvnrlesgvPSRFSGSGSGTEFTLTVSSLQPEDFATYS 87
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGG----KLLAE---------SGRFSVSRSGSTSTLTISNVTPEDSGTYT 67

                           90
                   ....*....|....*....
8TOP_Z          88 CQQCGSVPYTFGqGTTLEI 106
Cdd:smart00410  68 CAATNSSGSASS-GTTLTV 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z          6 QSPSSLSASVGDRVTITCRASQDISS---FLNWYQQKPGKAPKLLI--SSVNRLESGVPSRFSGSG--SGTEFTLTVSSL 78
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEastSVYWYRQPPGKGPTFLIayYSNGSEEGVKKGRFSGRGdpSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
8TOP_Z         79 QPEDFATYSCQQCGSVPYTFGQGTTLEI 106
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      113 PSVFIFPPSEDQV-KSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSkDNTYSLSSTLTLSSTEYQSHKV 191
Cdd:cd05847   1 PTVQILHSSCASTlTSETIQLLCLISGYTPSTIEVEWLVDGQVATLSAASTAPQKEE-GGTFSTTSKLNVTQEDWKSGKT 79

                        90
                ....*....|
8TOP_Z      192 YACEVTHQGL 201
Cdd:cd05847  80 YTCKVTHQGT 89

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      113 PSVFIFPPS-EDQVKSGTVSVVCLLNNFYPREASVKWKVDG-ALKTGNSQESVTEQDSKDNTYSLSSTLTLSSTEYQSHK 190
Cdd:cd16093   2 PTVSLHAPSrEEFLGNRTATFVCLATGFSPKTISFKWLRNGkEVTSSTGAVVEEPKEDGKTLYSATSFLTITESEWKSQT 81

                        90
                ....*....|.
8TOP_Z      191 VYACEVTHQGL 201
Cdd:cd16093  82 EFTCEFKHKGE 92

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z        5 TQSPSSLSASVGDRVTITCRASQDISSF-LNWYQQKPG-KAPKLLISSVNRLESGVPSRFSGS--GSGTEFTLTVSSLQP 80
Cdd:cd16088   3 TFSPALLVVTEGANATFTCSFSNTSESFvLNWYRLSPSnQTDKLAAFPEDRSQPGQDWRFRVTqlPNGRDFHMSVVRARR 82

                ....*...
8TOP_Z       81 EDFATYSC 88
Cdd:cd16088  83 NDSGTYLC 90

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, delta, epsilon, gamma, and mu chains; 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, delta, 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      112 APSVFIFPPSEDQVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSKDNTYSLSSTLTLSSTEYQSHKV 191
Cdd:cd04985   1 APTVFPLQSATKSQSNGPVALGCLISDYFPESITVSWQKNTNSITSGFTRTFPVVLRSGGDYSCSSQLTVPLQEWNSGEV 80

                        90
                ....*....|....*.
8TOP_Z      192 YACEVTHQGLSSPVTK 207
Cdd:cd04985  81 YKCQVQHSASNSKQEK 96

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) B and similar proteins; 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) B and similar proteins. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-B gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. Human leukocyte antigen (HLA) B*3501 (B35) is a common human allele involved in mediating protective immunity against HIV. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
8TOP_Z      134 CLLNNFYPREASVKWKVDGALKTGNSqESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21026  24 CWALGFYPAEITLTWQRDGEDQTQDT-ELVETRPAGDRTFQKWAAVVVPSGEEQR---YTCHVQHEGLPKPLT 92

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd; 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 H2-Dd. Mouse MHC is composed of 11 subclasses. It includes the classical MHC class I (MHC-Ia) that comprises H-2D, H-2K and H-2L subclasses, the non-classical MHC class I (MHCIb) that comprises H-2Q, H-2M and H-2T subclasses, the classical MHC class II (MHC-IIa) that includes H-2A(I-A) and H-2E(I-E) subclasses, and the non-classical MHC class II (MHC-IIb) comprises H-2M and H-2O. H-2K, H-2D, and H-2L are 80 to 90% homologous at the amino acid level yet appear to be involved in different recognition reactions and are differentially expressed on lymphoid cells. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
8TOP_Z      128 GTVSVVCLLNNFYPREASVKWKVDGALKTgNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21020  18 GDVTLRCWALGFYPADITLTWQLNGEELT-QEMELVETRPAGDGTFQKWASVVVPLGKEQK---YTCHVEHEGLPEPLT 92

Immunoglobulin (Ig) heavy chain (H), variable (V) domain; The members here are composed of the immunoglobulin (Ig) heavy chain (H), variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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 determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which can associate with any of the heavy chains. This family includes alpha, gamma, delta, epsilon, and mu heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z       16 GDRVTITCRASQDI--SSFLNWYQQKPGKAPKLL-----ISSVNRLESGVPSRFSGS--GSGTEFTLTVSSLQPEDFATY 86
Cdd:cd04981  13 GQSLKLSCKASGFTftSYGMGWVRQAPGKGLEWIgliypGGGDTYYADSFKGRFTITrdTSKSTAYLQLNSLTSEDTAVY 92

                        90       100
                ....*....|....*....|...
8TOP_Z       87 SCQQCGSVPYTF-----GQGTTL 104
Cdd:cd04981  93 YCARGLGGYGYSyfdywGQGTTV 115

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A; 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) A. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-A gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. HLA-A2 is associated with spontaneous abortions, HIV, and Hodgkin lymphoma. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
8TOP_Z      134 CLLNNFYPREASVKWKVDGALKTGNSqESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21027  24 CWALSFYPAEITLTWQRDGEDQTQDT-ELVETRPAGDGTFQKWAAVVVPSGQEQR---YTCHVQHEGLPKPLT 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
8TOP_Z      128 GTVSVVCLLNNFYPREASVKWKVDGALKTgNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21016  18 GDVTLRCWALGFYPADITLTWQKDGEELT-QDMEFVETRPAGDGTFQKWAAVVVPLGKEQS---YTCHVYHEGLPEPLT 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
8TOP_Z      128 GTVSVVCLLNNFYPREASVKWKVDGALKTgNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21014  17 GAVTLRCWALGFYPADITLTWQLNGEELT-QDMELVETRPAGDGTFQKWASVVVPLGKEQN---YTCHVNHEGLPEPLT 91

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) I-E; 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) I-E. 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 molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play 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. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      113 PSVFIFPPSEDQVKSGTVsVVCLLNNFYPREASVKWKVDGAL-KTGNSQESVTEqdSKDNTYSLSSTLTLSSteyQSHKV 191
Cdd:cd20998   7 PTVTVYPTKTQPLEHHNL-LVCSVSDFYPGNIEVRWFRNGKEeKTGIVSTGLVR--NGDWTFQTLVMLETVP---QSGEV 80

                        90
                ....*....|....*
8TOP_Z      192 YACEVTHQGLSSPVT 206
Cdd:cd20998  81 YTCQVEHPSLTDPVT 95

First immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
8TOP_Z       16 GDRVTITCRASQDISSFLNW---YQQKP-GKAPKLLISSVNRLESGVPSRFSGSGSGTeFTLTVSSLQPEDFATYSCQ 89
Cdd:cd07690   9 GDTAELPCTASQKKSIQFHWknsNQIKIlGNQGSFLTKGPSKLNDRADSRRNLWDQGS-FPLIIKNLKIEDSDTYICE 85

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; 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 MIC-A and MIC-B. MIC-A and MIC-B are homologs that serve as stress-inducible antigens on epithelial and epithelially derived cells. Both serve as ligands for the widely expressed activating immunoreceptor NKG2D, a C-type lectin-like activating immunoreceptor. MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins. 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
8TOP_Z      124 QVKSGTVSVVCLLNNFYPREASVKWKVDGALKTGNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQG 200
Cdd:cd21017  13 EASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGTYQTWVATRICQGEEQR---FTCYMEHSG 86

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      113 PSVFIFPP-SEDQvkSGTVSVVCLLNNFYPREASVKWKVDGALKTGnSQESVTEQDSKDNTYSLSSTLTLSSteyQSHKV 191
Cdd:cd05766   4 PSVKVSPTkTGPL--EHPNLLVCSVTGFYPAEIEVKWFRNGQEETA-GVVSTELIPNGDWTFQILVMLETTP---RRGDV 77

                        90
                ....*....|....*
8TOP_Z      192 YACEVTHQGLSSPVT 206
Cdd:cd05766  78 YTCQVEHSSLQSPLT 92

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
8TOP_Z      128 GTVSVVCLLNNFYPREASVKWKVDGALKTgNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21018  18 GEVTLRCWALGFYPADITLTWQLNGEELT-QDMELVETRPAGDGTFQKWASVVVPLGKEQN---YTCRVYHEGLPEPLT 92

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1 and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1 and similar proteins. Qa-1 presents hydrophobic peptides including Qdm derived from the leader sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1 bound peptides derived from the TCR Vbeta8.2 of activated T cells also activates CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence but have several variations that could affect peptide binding to Qa-1 or TCR recognition. 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      119 PPSEDQVksgtvSVVCLLNNFYPREASVKWKVDGALKTgNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTH 198
Cdd:cd21013  13 PRSEGYV-----TLRCWALGFYPADITLTWQLNGEELT-QDMEFVETRPAGDGTFQKWASVVVPLGKEQK---YTCHVEH 83

                ....*...
8TOP_Z      199 QGLSSPVT 206
Cdd:cd21013  84 EGLPEPLT 91

H-2 class I histocompatibility complex TLA (thymus leukemia antigen); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the major histocompatibility complex (MHC) H-2 class I histocompatibility complex TLA (thymus leukemia antigen). The murine MHC class I histocompatibility TLA (Thymus leukemia antigen), which is encoded in the T region by T3 and T18 genes, is expressed mainly by intestinal epithelial cells and thymocytes. The murine TLAs are class I, beta-2-microglobulin-associated glycoproteins. The TLA function is not defined by antigen presentation, but rather by its relatively high affinity binding to CD8-alpha-alpha compared with CD8-alpha-beta. The existence of a human homolog for murine TLA remains unresolved. This group is a member of the C1-set Ig domains, which 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
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8TOP_Z      128 GTVSVVCLLNNFYPREASVKWKVDGAlKTGNSQESVTEQDSKDNTYSLSSTLTLSSTEYQShkvYACEVTHQGLSSPVT 206
Cdd:cd21012  18 GYVTLRCWALGFYPAHITLTWQLNGE-ELIQDTELVETRPAGDGTFQKWAAVVVPSGEEQK---YTCHVYHEGLPEPLT 92

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; 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) DR. HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. HLA-DR is also involved in several autoimmune conditions, disease susceptibility, and disease resistance including seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, schizophrenia, Goodpasture syndrome, systemic lupus erythematosus, Alzheimers, tuberculoid leprosy, and Hashimoto's thyroiditis. HLA-DR molecules are upregulated in response to signaling. HLA-DR is an alphabeta heterodimer cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain, and a cytoplasmic tail. Both alpha and beta chains are anchored in the membrane. The DR beta chain is encoded by 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus, DRB1*. The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. 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). 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
8TOP_Z      113 PSVFIFPPSEDQVKSGTVsVVCLLNNFYPREASVKW------KVDGALKTGNSQESvteqdskDNTYSLSSTLTLSStey 186
Cdd:cd21000   4 PKVTVYPAKTQPLQHHNL-LVCSVNGFYPGSIEVRWfrngqeEKAGVVSTGLIQNG-------DWTFQTLVMLETVP--- 72

                        90       100
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8TOP_Z      187 QSHKVYACEVTHQGLSSPVT 206
Cdd:cd21000  73 RSGEVYTCQVEHPSVTSPLT 92

Class I major histocompatibility complex (MHC) alpha chain, alpha3 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 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.

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8TOP_Z      127 SGTVSVVCLLNNFYPREASVKWKVDGaLKTGNSQESVTEQDSKDNTYSLSSTLTLSSTEYQshkVYACEVTHQGLSSPVT 206
Cdd:cd07698  14 DGESTLRCWALGFYPAEITLTWQRDG-EDQTQDMELVETRPNGDGTFQKWAAVVVPSGEEQ---RYTCHVQHEGLPEPLT 89

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.