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Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides.

Granados DP, Sriranganadane D, Daouda T, Zieger A, Laumont CM, Caron-Lizotte O, Boucher G, Hardy MP, Gendron P, Côté C, Lemieux S, Thibault P, Perreault C

1] Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7 [2] Department of Medicine, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7 [3].

For decades, the global impact of genomic polymorphisms on the repertoire of peptides presented by major histocompatibility complex (MHC) has remained a matter of speculation. Here we present a novel approach that enables high-throughput discovery of polymorphic MHC class I-associated peptides (MIPs), which play a major role in allorecognition. On the basis of comprehensive analyses of the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings, we show that 0.5% of non-synonymous single nucleotide variations are represented in the MIP repertoire. The 34 polymorphic MIPs found in our subjects are encoded by bi-allelic loci with dominant and recessive alleles. Our analyses show that, at the population level, 12% of the MIP-coding exome is polymorphic. Our method provides fundamental insights into the relationship between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens).

Nat Commun 2014;5:3600.

Pubmed ID: 24714562

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