Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity.

ABSTRACT: The precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we can rapidly and accurately identify many HLA-I binding motifs and map them to their corresponding alleles without any a priori knowledge of HLA-I binding specificity. Our approach recapitulates and refines known motifs for 43 of the most frequent alleles, uncovers new motifs for 9 alleles that up to now had less than five known ligands and provides a scalable framework to incorporate additional HLA

SUBMITTER: Bassani-Sternberg M 

PROVIDER: S-EPMC5584980 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature