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

We developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses. Overall design: RNA-seq of human B lymphoblasts derived from peripheral blood mononuclear cells from 2 HLA-identical female siblings.