MHC polymorphism and parasites

  • Jan Klein
  • Colm O’huigin


The major histocompatibility complex (MHC) polymorphism is marked by the existence of allelic lineages that are extremely old, having been passed from one species to another in an evolutionary line of descent. Each species has several of these lineages and many of their more recent derivatives, the actual alleles. The lineages are separated by large genetic distances and are characterized by the presence of short sequence motifs which, at the protein level, have remained virtually unaltered for over 40 million years. Several explanations for the MHC polymorphism have been proposed. We argue that the only one consistent with the entire body of knowledge about the MHC is an explanation based on the immune response to parasites. Furthermore, we propose that parasites coevolving with their hosts have had a major influence on MHC polymorphism, whereas parasites that switched hosts recently and became very virulent have had little effect. The latter category includes micro- and macroparasites responsible for the major human infectious diseases. This hypothesis explains why no convincing association between human leucocyte antigen (HLA) alleles and resistance to infectious disease can thus far be documented, and indicates the direction in which the search for such associations should be taken.


Major Histocompatibility Complex Cerebral Malaria Major Histocompatibility Complex Molecule Major Histocompatibility Complex Gene Major Histocompatibility Complex Allele 
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Copyright information

© The Royal Society 1997

Authors and Affiliations

  • Jan Klein
    • 1
    • 2
  • Colm O’huigin
    • 1
  1. 1.Max-Planck-Institut für BiologieAbteilung ImmungenetikTübingenGermany
  2. 2.Department of Microbiology and ImmunologyUniversity of Miami School of MedicineMiamiUSA

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