The ABCs of MHC

The major histocompatibility complex (MHC) contains the most diverse genes known in vertebrates. These genes encode cell‐surface molecules that play a central role in controlling immunological activity and, as a consequence, in tissue rejection, autoimmunity, and immune responses to infectious diseases. In vertebrates, there are many different MHC genes, most with many alleles. This is true for all primates studied thus far. Multiple loci and alleles allow for an increased peptide‐binding repertoire; their variety has a profound impact on an organism's ability to battle constantly evolving pathogens. The argument that infectious disease is a driving force for MHC variability is supported by observations that most of the allelic variation centers on the amino acid residues that directly interact with foreign peptides. However, while MHC diversity could be maintained through heterozygote advantage, frequency‐dependent selection, or both, the direct evidence that natural selection enhances diversity is limited. Indeed, it is not wholly clear whether selection operates only with respect to disease resistance or if behavioral and biological mechanisms also contribute to the extreme variation that has been observed for many species. Furthermore, reproductive behavior and biology may also help to maintain genetic variability at MHC loci.