Immune System Genetics

The T cell-MHC interaction serves another, related function: It confirms that the cell is part of the self that the immune system should be protecting. Thus, MHCs serve as self-recognition markers. When a T cell recognizes foreign MHCs, as would occur in an organ transplant, it sets in motion an immune attack to reject the foreign tissue. Indeed, "histocompatibility" means compatibility of tissues, and these proteins control that process.

Somatic recombination in a B cell brings together a V segment and a J segment, both chosen at random. Intervening V and J segments are removed and degraded. Upstream V segments are not transcribed because their promoters are not close enough to the enhancer. Downstream J segments are transcribed but removed during RNA processing. The remaining V and J segments each code for part of the variable region of the antibody, while the C segment codes for the constant region.

There are two major classes of MHC proteins, called class I and II, with different functions in antigen presentation. Class I contains three members, each coded for by different genes, and class II contains four members. For almost every gene, there are multiple alleles. The number of alleles per gene ranges from a handful to more than 100. Since each person will inherit and express a unique set of MHC alleles, once again we can see the combinatorial possibilities: There are millions of different combinations of MHC alleles, and very few people are likely to have exactly the same set. This is what makes organ transplants so difficult. Matching MHC types is the key to success, but even close relatives may have different allele sets.