Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands.

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands. Mol Cell Proteomics. 2019 Dec 17;: Authors: Solleder M, Guillaume P, Racle J, Michaux J, Pak HS, Müller M, Coukos G, Bassani-Sternberg M, Gfeller D Abstract The presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition of infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing or aberrant post-translational modifications. Identifying HLA-I ligands remains a challenging task that requires either heavy experimental work for in-vivo identification or optimized bioinformatics tools for accurate predictions. To date, no HLA-I ligand predictor includes post-translational modifications. To fill this gap, we curated phosphorylated HLA-I ligands from several immunopeptidomics studies (including six newly measured samples) covering 72 HLA-I alleles, and retrieved a total of 2,066 unique phosphorylated peptides. We then expanded our motif deconvolution tool to identify precise binding motifs of phosphorylated HLA-I ligands. Our results reveal a clear enrichment of phosphorylated peptides among HLA-C ligands and demonstrate a prevalent role of both HLA-I motifs and kinase motifs on the presentation of phosphorylated peptides. These data ...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research