What is Major histocompatibility complex (MHC) and what does it do?
The Major histocompatibility complex encodes the human leukocyte antigens (HLAs). MHC and HLA are often used interchangeably.
There are three different classes—types I, II, and III. All are encoded on the short arm of chromosome 6 over a region of approximately 4 million base pairs. Class I and II molecules function to present antigens to T cells. There are over 1100 common polymorphisms of class I and II molecules in the general population. For the MHC class I region, over 200, 300, and 100 alleles have been identified for HLA-A, HLA-B, and HLA-C loci, respectively. Other class I genes (HLA-E, HLA-F, HLA-G) have limited function and polymorphisms. For the MHC class II region, over 250, 50, and 60 alleles have been identified for HLA-DRβ, HLA-DQ, and HLA-DP loci, respectively. Other genes in the class II region are involved in peptide processing, which includes peptide sizing (proteasome subunits LMP1 and 2), peptide transport (TAP1 and 2), and peptide loading onto class II molecules (DMA, DMB, DO/DN). The remainder of the MHC complex stretches between the class I and II regions and encodes various proteins that are not capable of presenting antigen. However, many of these MHC class III proteins are involved in the regulation of the immune response, and some have rheumatic disease associations. These include C2, C4A and C4B, and factor B of the complement system; TNFα and lymphotoxin; and some of the HSPs. Both MHC class I and II molecules are dimers. While the MHC encodes both α- and β-chains of class II molecules, it encodes only MHC class I α-chain. β 2 -microglobulin, the β-chain shared by all MHC class I molecules, is encoded by a relatively invariant allele on chromosome 15. Note that in spite of the large number of HLA polymorphisms, each individual only codominantly inherits one allele at each locus from each parent, that is, two HLA-A alleles (one from father and one from mother), two HLA-B alleles, and so on. Figure 4.3 summarizes the structure of Chromosomes 6 and 15 with the MHC genes.