InterPro domain: IPR011162

Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.

This superfamily represents MHC class I and II-like antigen-recognition domains from:

• MHC class II, N-terminal domains of alpha and beta chains [ 1 ]
• MHC class I, alpha-1 and alpha-2 domains [ 2 ]
• MHC class I related proteins, such as gammadelta T-cell ligand [ 3 ], Ulbp3 [ 4 ], Fc (IgG) receptor (alpha-1 and -2 domains) [ 5 ], CD1 (alpha-1 and -2 domains) [ 6 ], zinc-alpha-2-glycoprotein ZAG (fat depleting factor) [ 7 ]
• Immunomodulatory protein m144, alpha-1 and alpha-2 domains [ 8 ]
• Haemochromatosis protein Hfe, alpha-1 and alpha-2 domains [ 9 ]
• NK cell ligand RAE-1 beta [ 10 ]
• Endothelial protein C receptor (phospholipid-binding protein) [ 11 ]

1. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation. Immunity 9, 377-83
2. Conformational flexibility of the MHC class I alpha1-alpha2 domain in peptide bound and free states: a molecular dynamics simulation study. Biophys. J. 87, 2203-14
3. Antigen recognition by gammadelta T cells. Immunol. Rev. 215, 46-58
4. Structure and function of natural-killer-cell receptors. Immunol. Res. 27, 539-48
5. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature 372, 379-83
6. Genomic and phylogenetic analysis of the human CD1 and HLA class I multicopy genes. J. Mol. Evol. 53, 642-50
7. Zn-alpha2-glycoprotein, an MHC class I-related glycoprotein regulator of adipose tissues: modification or abrogation of ligand binding by site-directed mutagenesis. Biochemistry 45, 2035-41
8. Crystal structure of the murine cytomegalovirus MHC-I homolog m144. J. Mol. Biol. 358, 157-71
9. Evidence for the interaction of the hereditary haemochromatosis protein, HFE, with the transferrin receptor in endocytic compartments. Biochem. J. 373, 145-53
10. Natural killer cell-mediated lysis of dorsal root ganglia neurons via RAE1/NKG2D interactions. Eur. J. Immunol. 33, 92-100
11. Endothelial cell protein C receptor acts as a cellular receptor for factor VIIa on endothelium. J. Biol. Chem. 282, 11849-57