Unraveling the glycosylated immunopeptidome with HLA-Glyco

Georges Bedran, Daniel A. Polasky, Yi Hsiao, Fengchao Yu, Felipe da Veiga Leprevost, Javier A. Alfaro, Marcin Cieslik, Alexey I. Nesvizhskii*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Recent interest in targeted therapies has been sparked by the study of MHC-associated peptides (MAPs) that undergo post-translational modifications (PTMs), particularly glycosylation. In this study, we introduce a fast computational workflow that merges the MSFragger-Glyco search algorithm with a false discovery rate control for glycopeptide analysis from mass spectrometry-based immunopeptidome data. By analyzing eight large-scale publicly available studies, we find that glycosylated MAPs are predominantly presented by MHC class II. Here, we present HLA-Glyco, a comprehensive resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights, including high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between HLA allele groups. We integrate the workflow within the FragPipe computational platform and provide HLA-Glyco as a free web resource. Overall, our work provides a valuable tool and resource to aid the nascent field of glyco-immunopeptidomics.
Original languageEnglish
Article number3461
Pages (from-to)1-12
JournalNature Communications
Issue number1
Publication statusPublished - 12 Jun 2023


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