MHC-I family domain;

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2462515246   6 CKVLNQNQHENDITHNLLSDTCPRFILGLLDAGKA 40
Cdd:pfam16497 145 CKVLNQDQGTKETVQWLLSDTCPRFVLGLLEAGKA 179

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515246   62 HLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAA---GEAADLSCRVKHSSL 129
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRnGQEVTEGVSTTDPLKNSDGTYFLSSYLTVPAstwESGDVYTCQVTHEGL 72

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  57 SPGPGHLQ----LVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAAD---LSCRVKHSS 128
Cdd:pfam07654   5 PPSPEELGkpntLTCLVTGFYPPDITVTWLKnGQEVTEGVKTTPPSPNSDWTYQLSSYLTVTPSDWESgdeYTCRVEHEG 84

                  .
gi 2462515246 129 L 129
Cdd:pfam07654  85 L 85

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515246   62 HLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAA---GEAADLSCRVKHSSL 129
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRnGQEVTEGVSTTDPLKNSDGTYFLSSYLTVPAstwESGDVYTCQVTHEGL 72

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 2462515246  49 EAWLSHGPSP--GPGHLQLVCHVSGFYPKPVWVMWMRGEQEQQ-GTQRGDILPSADGTWYLRATLEVAAG---EAADLSC 122
Cdd:cd00098     1 TVTLLPPSPEekGGGKVTLVCLVSGFYPKDITVTWLKNGVPLTsGVSTSSPVEPNDGTYSVTSSLTVPPSdwdEGATYTC 80

                          90
                  ....*....|....*.
gi 2462515246 123 RVKHSSLEgQDIVLYW 138
Cdd:cd00098    81 VVTHESLK-SPLSKTW 95

Immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG). ZAG is a soluble protein that is present in serum and other body fluids. ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. The 2.8 angstrom crystal structure of ZAG resembles a class I major histocompatibility complex (MHC) heavy chain, but ZAG does not bind the class I light chain beta-2-microglobulin. The ZAG structure includes a large groove analogous to class I MHC peptide binding grooves. Instead of a peptide, the ZAG groove contains a nonpeptidic compound that may be implicated in lipid catabolism under normal or pathological conditions. IgC_MHC_I_alpha3; 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  53 SHGpspGPGHLQ-LVCHVSGFYPKPVWVMWMRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLeG 131
Cdd:cd21010    11 SHV---APGKNRtLKCLAYDFYPRGISLHWTRAGKVQESESGGDVLPSGNGTYQSWVVVEVPPQDRAPYSCHVEHSSL-A 86

                  ....*..
gi 2462515246 132 QDIVLYW 138
Cdd:cd21010    87 QPLTVPW 93

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; 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 alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  43 QRQVKPEAWLSHGPSpGPGHLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLS 121
Cdd:cd21023     1 QRADPPKAHVAHHPI-SDHEATLRCWALGFYPAEITLTWQRdGEEQTQDTELVETRPAGDGTFQKWAAVVVPPGEEQRYT 79

                          90
                  ....*....|....*....
gi 2462515246 122 CRVKHSSLEgQDIVLYWEH 140
Cdd:cd21023    80 CHVQHEGLP-QPLILRWEQ 97

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515246  62 HLQLVCHVSGFYPKPVWVMWMRGEQEQ-QGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEG 131
Cdd:cd05766    19 PNLLVCSVTGFYPAEIEVKWFRNGQEEtAGVVSTELIPNGDWTFQILVMLETTPRRGDVYTCQVEHSSLQS 89

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515246  65 LVCHVSGFYPKPVWVMWMR---GEQEQQGTQRGDILPS----ADGTWYLRATLEVAAGEA---ADLSCRVKHSSLE 130
Cdd:cd05771    19 LSCHIAGYYPLDVDVEWLReepGGSESQVSRDGVSLSShrqsVDGTYSISSYLTLEPGTEnrgATYTCRVTHVSLE 94

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  44 RQVKPEAWLSHGPSpGPGHLQLVCHVSGFYPKPVWVMW-MRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSC 122
Cdd:cd21013     1 RSDPPKAHVTHHPR-SEGYVTLRCWALGFYPADITLTWqLNGEELTQDMEFVETRPAGDGTFQKWASVVVPLGKEQKYTC 79

                          90
                  ....*....|....*..
gi 2462515246 123 RVKHSSLEgQDIVLYWE 139
Cdd:cd21013    80 HVEHEGLP-EPLTLRWE 95

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; 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 H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  44 RQVKPEAWLSHGPSPGPGHLQlvCHVSGFYPKPVWVMWMRGEQ--EQQGTQRGDILPSADGTWYLRATLEVAAGEAADLS 121
Cdd:cd21021     1 QQVPPLVKVTHHVTSSVTTLR--CRALNYYPQNITMKWLKDKQpmDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYT 78

                          90
                  ....*....|....*..
gi 2462515246 122 CRVKHSSLEgQDIVLYW 138
Cdd:cd21021    79 CQVEHPGLD-QPLIVIW 94

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1b; member of the C1-set of Ig superfamily (IgSF) domains; The non-classical mouse MHC class I (MHC-I) molecule Qa-1b is a non-polymorphic MHC molecule with an important function in innate immunity. It binds and presents signal peptides of classical MHC-I molecules at the cell surface and, as such, act as an indirect sensor for the normal expression of MHC-I molecules. This signal peptide dominantly accommodated in the groove of Qa-1b is called Qdm, for Qa-1 determinant modifier, and its amino acid sequence AMAPRTLLL is highly conserved among mammalian species. The Qdm/Qa-1b complex serves as a ligand for the germ-line encoded heterodimeric CD94/NKG2A receptors expressed on natural killer (NK) cells and activated CD8+ T cells and transduces inhibitory signals to these lymphocytes. Thus, upon binding, Qa-1b signals NK cells not to engage in cell lysis. The molecular basis of Qa-1b function is unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  43 QRQVKPEAWLSHGPSpGPGHLQLVCHVSGFYPKPVWVMW-MRGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLS 121
Cdd:cd21820     1 QRSDPPKAHVTHHPR-SEDEVTLRCWALGFYPADITLTWqLNGEELTQDMELVETRPAGDGTFQKWAAVVVPLGKEQYYT 79

                          90
                  ....*....|....*...
gi 2462515246 122 CRVKHSSLEgQDIVLYWE 139
Cdd:cd21820    80 CHVYHEGLP-EPLTLRWE 96

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515246  61 GHLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQR-GDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEG 131
Cdd:cd21017    17 GNITVTCRASGFYPWNITLSWRQdGVSLSHDTQQwGDVLPDGNGTYQTWVATRICQGEEQRFTCYMEHSGNHS 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515246  62 HLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSL 129
Cdd:cd21000    19 HNLLVCSVNGFYPGSIEVRWFRnGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSV 87

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  36 DAGKAHLQRQVKPEawlshgpspgpGHLQLVCHVSGFYPKPVWVMW-MRGEQEQQGTQRGDILPSADGTWYLRATLEVAA 114
Cdd:cd21020     4 DPPKAHVTHHRRPE-----------GDVTLRCWALGFYPADITLTWqLNGEELTQEMELVETRPAGDGTFQKWASVVVPL 72

                          90       100
                  ....*....|....*....|....
gi 2462515246 115 GEAADLSCRVKHSSLEgQDIVLYW 138
Cdd:cd21020    73 GKEQKYTCHVEHEGLP-EPLTLRW 95

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 2462515246  65 LVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEgQDIVLYW 138
Cdd:cd21022    21 LRCWALGFYPAEIILTWQRdGEDQTQDVELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLP-EPLMLRW 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  62 HLQLVCHVSGFYPKPVWVMWMRGEQEQQ-GTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLE 130
Cdd:cd21001    19 HNLLVCSVTDFYPGQIKVRWFRNDQEETaGVVSTPLIRNGDWTFQILVMLEMTPQRGDVYTCHVEHPSLQ 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515246  58 PGPGHLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSL 129
Cdd:cd20998    18 PLEHHNLLVCSVSDFYPGNIEVRWFRnGKEEKTGIVSTGLVRNGDWTFQTLVMLETVPQSGEVYTCQVEHPSL 90

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) E; 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) E. HLA-E is the first human class Ib major histocompatibility complex molecule to be crystallized. Like other MHC class I molecules, HLA-E is a heterodimer consisting of an a heavy chain and light chain beta-2-microglobulin. HLA-E is highly conserved and almost nonpolymorphic, and has recently been shown to be the first specialized ligand for natural killer cell receptors. 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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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  48 PEAWLSHGPSpGPGHLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKH 126
Cdd:cd21024     6 PKTHVTHHPI-SDHEATLRCWALGFYPAEITLTWQQdGEGHTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQH 84

                          90
                  ....*....|..
gi 2462515246 127 SSLEgQDIVLYW 138
Cdd:cd21024    85 EGLP-EPVTLRW 95

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  43 QRQVKPEAWLSHGpSPGPGHLQLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLS 121
Cdd:cd21027     1 QRTDAPKTHMTHH-AVSDHEATLRCWALSFYPAEITLTWQRdGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYT 79

                          90
                  ....*....|....*..
gi 2462515246 122 CRVKHSSLEgQDIVLYW 138
Cdd:cd21027    80 CHVQHEGLP-KPLTLRW 95

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515246  65 LVCHVSGFYPKPVWVMWM-RGEQEQQGTQRGDILPSADGTWYLRATLEVAAGEA---ADLSCRVKHSSL 129
Cdd:cd07699    21 LVCLINKFYPGFATVTWKvDGSTVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWnkhKVYTCEVTHEGL 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515246  64 QLVCHVSGFYPKPVWVMWMR-GEQEQQGTQRGDILPSADGTWYLRAT--LEVAAGE---AADLSCRVKHSSL 129
Cdd:cd16093    21 TFVCLATGFSPKTISFKWLRnGKEVTSSTGAVVEEPKEDGKTLYSATsfLTITESEwksQTEFTCEFKHKGE 92

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515246  57 SPGPGHLQLVCHVSGFYPKPVWVMWMRGEQEQ-QGTQRGdiLPSA---DGTWYLRATLEVAA---GEAADLSCRVKHSS 128
Cdd:cd04985    13 SQSNGPVALGCLISDYFPESITVSWQKNTNSItSGFTRT--FPVVlrsGGDYSCSSQLTVPLqewNSGEVYKCQVQHSA 89

Signal-regulatory protein (SIRP) immunoglobulin-like domain 2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 2 (C1 repeat 1). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains, a single V-set and two C1-set IgSF domains. Their cytoplasmic tails contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47, but with much less affinity.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  47 KPEAWLSHGPSP--GPGH-LQLVCHVSGFYPKPVWVMWMRGEQEQQGTQRgDILPSADGTWY-LRATLEVAAGEA---AD 119
Cdd:cd05772     1 KPSQPLVSGPSGraTPGQtVSFTCKSHGFSPRDITLKWFKNGNELSALQT-TVFPEGDSVSYsVSSTVQVVLTKDdvhSQ 79

                          90
                  ....*....|..
gi 2462515246 120 LSCRVKHSSLEG 131
Cdd:cd05772    80 LTCEVAHVTLQA 91

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515246  48 PEAWLSHGPSPGPGH---LQLVCHVSGFYPKPVWVMWMRGEQEqqgtqrGDILPS-------ADGTWYLRATLEVAAGEA 117
Cdd:cd05847     1 PTVQILHSSCASTLTsetIQLLCLISGYTPSTIEVEWLVDGQV------ATLSAAstapqkeEGGTFSTTSKLNVTQEDW 74

                          90
                  ....*....|....*....
gi 2462515246 118 AD---LSCRVKHSSLEGQD 133
Cdd:cd05847    75 KSgktYTCKVTHQGTTFEA 93