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Scientific article
Open access
English

HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection

Published inImmunogenetics, vol. 68, no. 6-7, p. 401-416
Publication date2016
Abstract

The main function of HLA class I molecules is to present pathogen-derived peptides to cytotoxic T lymphocytes. This function is assumed to drive the maintenance of an extraordinary amount of polymorphism at each HLA locus, providing an immune advantage to heterozygote individuals capable to present larger repertories of peptides than homozygotes. This seems contradictory, however, with a reduced diversity at individual HLA loci exhibited by some isolated populations. This study shows that the level of functional diversity predicted for the two HLA-A and HLA-B genes considered simultaneously is similar (almost invariant) between 46 human populations, even when a reduced diversity exists at each locus. We thus propose that HLA-A and HLA-B evolved through a model of joint divergent asymmetric selection conferring all populations an equivalent immune potential. The distinct pattern observed for HLA-C is explained by its functional evolution towards killer cell immunoglobulin-like receptor (KIR) activity regulation rather than peptide presentation.

Keywords
  • HLA class I polymorphism
  • Functional variation
  • Peptide-binding properties
  • Asymmetric balancing selection
  • Heterozygous advantage
  • Immune protection
Citation (ISO format)
BUHLER, Stéphane, NUNES, Jose Manuel, SANCHEZ-MAZAS, Alicia. HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection. In: Immunogenetics, 2016, vol. 68, n° 6-7, p. 401–416. doi: 10.1007/s00251-016-0918-x
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0093-7711
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