Was the ancestral MHC involved in innate immunity
2010
Levasseur, Anthony | Pontarotti, Pierre | Unité mixte de recherche de biotechnologie des champignons filamenteux ; Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Université de Provence - Aix-Marseille 1 | Centre National de la Recherche Scientifique (CNRS)
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Show more [+] Less [-]English. Understanding the nature of MHC class I presentation preferences is a challenging prospect. Large sets of peptide–MHC-class I complexes have been screened for their binding affinities and recent studies have shown that HLA-A share a preference for binding peptides derived from pathogens; however, no mechanism explaining the observed preferences has been demonstrated so far. In this issue of the European Journal of Immunology, a study demonstrates that HLA-A, but not HLA-B, preferentially recognises peptides enriched in amino acids encoded by sequences with low G+C content, and therefore recognises peptides associated with pathogens – low G+C content being a general feature of lower organisms. The authors of the study provide exciting results contributing to the understanding of the nature of MHC-I presentation preferences and MHC-I evolution. Although significant results are presented by the authors, here, we challenge the interpretation whereby HLA-A has been evolutionarily selected for such a function and appeal for the use of comparative phylogenetic methods to substantiate it. We propose a method to ascertain whether ancestral MHC recognised peptides from pathogens and hence was involved in the non-specific recognition of such organisms. Moreover, we suggest that ancestral MHC may have been involved in innate immune responses before being recruited for adaptive immunity
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