The HLA ligandome comprises a limited repertoire of O-GlcNAcylated antigens preferentially associated with HLA-B07:02

ABSTRACT: Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neo-antigens and peptide antigens harbouring post-translational modifications. Here we concentrate on the latter, focusing on the small subset of HLA Class I peptides (less than 1%) that has been observed to be post-translationally modified (PTM) by a O-linked N-acetylglucosamine (GlcNAc). Just like neo-antigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from JY B cell lymphoblastoid line cells, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. The cumulative list of O-GlcNAcylated HLA peptides originates from diverse datasets, entailing normal and cancer cell lines as well as tissue samples. Interestingly, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. From the compiled list we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B07:02 allele. This allele accommodates a Proline anchoring site at position 2, and a binding groove that can accommodate the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T). Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. The conclusions drawn from the compiled list, may assist to predict novel O-GlcNAcylated HLA antigens, which will likely be presented best by patients harbouring HLA-B7:02, or related, alleles that uses Proline as anchoring residue.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Suspension Culture

SUBMITTER: Alvaro Sanchez Bernabeu  

LAB HEAD: Albert JR Heck

PROVIDER: PXD028874 | Pride | 2021-12-03

REPOSITORIES: Pride