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

Authors
  • Granados, Diana Paola
  • Sriranganadane, Dev
  • Daouda, Tariq
  • Zieger, Antoine
  • Laumont, Céline M
  • Caron-Lizotte, Olivier
  • Boucher, Geneviève
  • Hardy, Marie-Pierre
  • Gendron, Patrick
  • Côté, Caroline
  • Lemieux, Sébastien
  • Thibault, Pierre
  • Perreault, Claude
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Publication Date
Jan 01, 2014
Volume
5
Pages
3600–3600
Identifiers
DOI: 10.1038/ncomms4600
PMID: 24714562
Source
Medline
License
Unknown

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).

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