Genetics of MHC

The Major Histocompatibility Complex (MHC) is a gene rich region encoding highly polymorphic histocompatibility genes. These were first discovered and studied in graft rejection experiments. Work in this area attempts to match organ donors and recipients for the antigens important for successful transplantations. The human MHC, also known as HLA, consists of approximately 4,000 kilobases of DNA covering about 2.5 map units located on the short arm of chromosome 6. Many proteins encoded in this region are involved is diverse aspects of the immunological response mechanism.

MHC gene locii

The MHC class I locus contains smaller loci for the classical genes, named A, B and C and non-classical genes E, F and G. All code for class I molecules, but each is distinct in its structure and binding capacity. The class I gene codes only for the alpha protein of the Class I molecule. The beta-2 microglobulin gene is very constant and is located elsewhere in the genome.

A similar situation exists for MHC II, where the locus is split into three smaller loci named DP, DQ and DR. Here each gene codes for a variant of both the alpha and beta protein. Since it is possible for an alpha unit from one gene to associate with a beta of another, there are a maximum of twelve different MHC II molecules. The prevalence of different HLA types vary widely in different populations. It is within this region that the genes for LMP proteins and TAP transporters have been found.

The region between the D and B loci codes for a number of MHC class III proteins, including the complement components C2, C4 and Factor B.
(The diagram above indicates the positions of the markers Ke3, Bat1 and Mog.)

Suggested further reading

Roberto S. Accolla
MHC and the immune response.

Omim Entry [142880]