Major Histocompatibility Complex: Human


The major histocompatibility complex (MHC) is a large genetic region that contains the most polymorphic loci known in humans and other vertebrates. MHC genes are the most intensively studied genes because they influence so many important traits, including resistance to infectious diseases, autoimmunity, compatibility of tissue transplants, spontaneous abortion, odour and mating preferences.

Keywords: human leucocyte antigen (HLA); tissue rejection; genetics and disease resistance; host–parasite coevolution; mating preferences; spontaneous abortion

Figure 1.

Simplified map of the genetic organization of the HLA complex. The principal class‐I genes are represented by ovals and class‐II genes by thick rectangles. The classical class‐I and class‐II HLA genes are indicated by green, whereas nonclassical ones by blue. The TAP and LMP genes, and tapasin‐encoding gene within the class‐II region are shown by red thin rectangles. Within the class‐III region only the genes encoding complement proteins are shown by yellow short rectangles.

Figure 2.

HLA alleles have extremely high polymorphisms at both (a) class I and (b) class II loci. The polymorphisms correspond to the antigen‐binding site of MHC molecules, which they encode. Data from European Bioinformatics Institute, April 2004 (

Figure 3.

HIV patients with more heterozygous HLA loci progress to HIV more slowly than those with more homozygous loci. Modified from Carrington M, Nelson GW, Martin MP et al. (1999) HLA and HIV‐1: heterozygote advantage and B*35‐Cw*04 disadvantage. Science283: 1748–1752.

Figure 4.

Couples sharing HLA haplotypes have longer interbirth intervals than other couples. Modified from Ober et al..

Figure 5.

Trans‐species polymorphisms. (a) For most human genes, the closest relative of an allelic variant is another human allele. This is because the diversity of most alleles arose after the evolutionary divergence of humans and chimpanzees. (b) However, with MHC genes, the closest resemblance is to a chimpanzee rather than a human allele. This suggests that the diversity of human MHC alleles is ancient, originating before the divergence of humans and chimpanzees.



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Further Reading

Lechler R and Warrens A (2000) HLA in Health and Disease. London: Academic Press.

Mayer D and Thomson G (2001) How selection shapes variation of the human major histocompatibility complex: a review. Annals of Human Genetics 65: 1–26.

Penn DJ (2002) The scent of genetic compatibility: sexual selection and the major histocompatibility complex. Ethology 108: 1–21.

Veenstra van Nieuwenhoven AL, Heineman MJ and Faas MM (2003) The immunology of successful pregnancy. Human Reproduction Update 9: 347–357.

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Penn, Dustin J, and Ilmonen, Petteri(Sep 2005) Major Histocompatibility Complex: Human. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0003987]