What is MHC Class I?

All class I genes are between 3 and 6 kb, the classical HLA antigens encoded in this region are HLA – A, B, and C. Class I HLA genes are highly polymorphic (multiple forms). There are at least 57 HLA-A alleles, 111 HLA-B alleles, and 34 HLA-C alleles.

HLA antigens are expressed on the surface of almost all cells and form functional receptors. They are important for displaying antigens of viruses or parasites to killer T-cells in cellular immunity.

The peptides that they present are produced from digested proteins that are broken down in the proteasomes inside the cell. Generally the peptides are small polymers of about 9 amino acids in length. Class I MHC is also particularly important in organ and tissue rejection following transplantation.

In addition to the portion of class I MHC, that was coded by the genes on chromosome 6, each class I MHC protein contains a small, non-variable protein component called beta 2-microglobulin also. It is coded by a gene on chromosome 15.

The 1998 Nomenclature Committee recognized more HLA genes, in class I and lb regions: they are HLA-E, -F, -G, -H, -J, -K and -L. Among those, only HLA-E, -F and -G are expressed antigens and are considered as minor histocompatible molecules.

Class I Molecules

Almost all the cells of an animal’s body have thousands of class I molecules present on the plasma membrane.

Class I molecules are composed of two polypeptide chains; one is heavy alpha (0) chain encoded by the BCA region and another is a light chain- beta-2-globulin (62-microglobulin) that is encoded elsewhere.

The MHC-encoded alpha chain is about 350 amino acids long and glycosylated, giving a total molecular weight of about 45 kDa. Alpha chain can be divided into three extra cellular domins, alphal, alpha 2 and alpha 3, in addition to a trans membrane domain, where the polypeptide chain passes through the plasma membrane of the cell; and a cytoplasmic domain (with the C terminal) within the cytoplasm of the cell.

The alpha 3 domain is highly conserved, as is beta- 2-microglobulin. Both alpha 3 domains and beta-2-microglobulin are homologous to the CH3 domain of human immunoglobulins. Except the alpha 3 domain, the remaining domains are stabilized by disulfide (S-S) bridges.

62-microglobulin is a 12 kDa polypeptide that is non-covalently associated with the alpha-3 domain. The 01 and 0 2 domains fold to make up a groove for peptides to bind. MHC class I molecule binds peptides that are 8-10 amino acid in length and present to a T-cell.

Without the beta-2 microglobulin, the class I antigen cannot be expressed on the cell surface. Individuals with a defective beta-2 microglobulin gene does not express any class I antigen and hence have a deficiency of cytotoxic T cell function.