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

Diana Paola Granados, Dev Sriranganadane, Tariq Daouda, Antoine Zieger, Céline M. Laumont, Olivier Caron-Lizotte, Geneviève Boucher, Marie-Pierre Hardy, Patrick Gendron, Caroline Côté, Sébastien Lemieux, Pierre Thibault () and Claude Perreault ()
Additional contact information
Diana Paola Granados: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Dev Sriranganadane: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Tariq Daouda: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Antoine Zieger: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Céline M. Laumont: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Olivier Caron-Lizotte: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Geneviève Boucher: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Marie-Pierre Hardy: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Patrick Gendron: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Caroline Côté: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Sébastien Lemieux: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Pierre Thibault: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
Claude Perreault: Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract 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).

Date: 2014
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DOI: 10.1038/ncomms4600

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