Avs. Hill et al., HUMAN-LEUKOCYTE ANTIGENS AND NATURAL-SELECTION BY MALARIA, Philosophical transactions-Royal Society of London. Biological sciences, 346(1317), 1994, pp. 379-385
The extraordinary polymorphism of human leukocyte antigens (KLA) poses
a question as to how this remarkable diversity arose and is maintaine
d. The explanation that infectious pathogens are largely responsible i
s theoretically attractive but clear and consistent associations betwe
en HLA alleles and major infectious diseases have rarely been identifi
ed. Large case-control studies of HLA types in African children with s
evere malaria indicate that HLA associations with this parasitic infec
tion do exist and it is becoming possible to investigate the underlyin
g mechanisms by identification of peptide epitopes in parasite antigen
s. Such analysis reveals how the magnitude and detectability of HLA as
sociations may be influenced by numerous genetic and environmental fac
tors. These complex interactions will give rise to variation over time
and space in the selective pressures exerted by infectious diseases a
nd this fluctuation may, in itself, contribute to the maintenance of H
LA polymorphism.