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The extraordinary polymorphism of human leukocyte antigens (HLA) poses a question as to how this remarkable diversity arose and is maintained. The explanation that infectious pathogens are largely responsible is theoretically attractive but clear and consistent associations between HLA alleles and major infectious diseases have rarely been identified. Large case-control studies of HLA types in African children with severe malaria indicate that HLA associations with this parasitic infection do exist and it is becoming possible to investigate the underlying mechanisms by identification of peptide epitopes in parasite antigens. Such analysis reveals how the magnitude and detectability of HLA associations may be influenced by numerous genetic and environmental factors. These complex interactions will give rise to variation over time and space in the selective pressures exerted by infectious diseases and this fluctuation may, in itself, contribute to the maintenance of HLA polymorphism.

Original publication

DOI

10.1098/rstb.1994.0155

Type

Journal article

Journal

Philos Trans R Soc Lond B Biol Sci

Publication Date

29/11/1994

Volume

346

Pages

379 - 385

Keywords

Biological Evolution, HLA Antigens, Host-Parasite Interactions, Humans, Leukocytes, Malaria, Polymorphism, Genetic, Selection, Genetic