| Reference |
|---|
| Reference Type | Literature | IEDB_Reference:1032297 |
| Title | Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity. | |
| Authors | Michal Bassani-Sternberg; Chloé Chong; Philippe Guillaume; Marthe Solleder; HuiSong Pak; Philippe O Gannon; Lana E Kandalaft; George Coukos; David Gfeller | |
| Affiliations | Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, Switzerland; Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. | |
| Journal | PLoS Comput Biol | |
| Year | 2017 | |
| 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 peptidomics studies in the future. The refined motifs improve neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA peptidomics data are ideal for in silico predictions of neo-antigens from tumor exome sequencing data. The new motifs further reveal distant modulation of the binding specificity at P2 for some HLA-I alleles by residues in the HLA-I binding site but outside of the B-pocket and we unravel the underlying mechanisms by protein structure analysis, mutagenesis and in vitro binding assays. | |
| Curation Last Updated | 2025-02-27 20:17:56 | |