Histocompatibility genes

Group of genes (gene complexes) encoding major histocompatibility bit antigens, HLA (also MHC or major histocompatibility bit antigens) In humans they are located on chromosome 6.

For class I HLA antigens, these are the sections HLA-A, HLA-B or HLA-C also called classical HLA I antigens and the sections HLA-E, HLA-F, HLA-G (non-classical HLA I antigens).

For class II HLA antigens these are the sections HLA-DP, HLA-DQ, HLA-DR (classical HLA II antigens) and HLA-DN, HLA-DM, HLA-DO (non-classical HLA II antigens).

Both class I and class II HLA genes exhibit a large allelic polymorphism (polygenic gene complexes), which is particularly pronounced in the area of the binding pits of the HLA molecule for peptides. Due to the polygenic gene complex, there are several subgene exons that, for example, encode the different peptide chains of the HLA molecules. The beta2 microglobulin, which is the 2nd chain of the HLA I molecule, is independently encoded on chromosome 15.

All HLA genes are highly polymorphic, i.e. multiple alleles are available. Polygenic and polymorphic diversity thus determine the enormous variability of HLA haplotypes. This variability of the HLA haplotypes determines the highly different configuration of the binding pits for peptide antigens, which the HLA complex recognizes, binds and presents to an immune cell (see antigen presentation below).

This, together with the diversity of T-cell receptor (TCR) specificities, contributes to an almost unlimited variety of adaptive immune responses. Individuals thus have a better or worse ability to bind certain peptides and specifically fend off antigens. Many autoimmune diseases are also associated with a specific HLA haplotype. HLA antigens are also decisive for the tolerance (histocompatibility) or intolerance of the tissues of two individuals, which plays a decisive role in transplantation surgery.