HLA Class I Molecular Variation and Peptide-binding Properties Suggest a Model of Joint Divergent Asymmetric Selection

Overview

Journal Immunogenetics

Specialties Allergy & Immunology
Genetics

Date 2016 May 29

PMID 27233953

Citations 23

Authors

Stephane Buhler

Jose Manuel Nunes

Alicia Sanchez-Mazas

Affiliations

Soon will be listed here.

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.

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