Cargando…
The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02
Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens and peptide antigens harbouring post-translational modifications. Here we concentrate on the latter, focusing...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671986/ https://www.ncbi.nlm.nih.gov/pubmed/34925382 http://dx.doi.org/10.3389/fimmu.2021.796584 |
_version_ | 1784615264629817344 |
---|---|
author | Mukherjee, Soumya Sanchez-Bernabeu, Alvaro Demmers, Laura C. Wu, Wei Heck, Albert J. R. |
author_facet | Mukherjee, Soumya Sanchez-Bernabeu, Alvaro Demmers, Laura C. Wu, Wei Heck, Albert J. R. |
author_sort | Mukherjee, Soumya |
collection | PubMed |
description | Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens 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 neoantigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from the JY B cell lymphoblastoid cell line, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. This cumulative list of O-GlcNAcylated HLA peptides were derived from normal and cancerous origin, as well as tissue specimen. Remarkably, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. From this list, we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B*07:02 allele. This allele loads peptides with a Proline residue anchor at position 2, and features a binding groove that can accommodate well the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T), essentially explaining why HLA-B*07:02 is a favoured binding allele. The observations drawn from the compiled list, may assist in the prediction of novel O-GlcNAcylated HLA antigens, which will be best presented by patients harbouring HLA-B*07:02 or related alleles that use Proline as anchoring residue. |
format | Online Article Text |
id | pubmed-8671986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86719862021-12-16 The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 Mukherjee, Soumya Sanchez-Bernabeu, Alvaro Demmers, Laura C. Wu, Wei Heck, Albert J. R. Front Immunol Immunology Mass-spectrometry based immunopeptidomics has provided unprecedented insights into antigen presentation, not only charting an enormous ligandome of self-antigens, but also cancer neoantigens 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 neoantigens these modified antigens may have specific immunomodulatory functions. Here we compiled from literature, and a new dataset originating from the JY B cell lymphoblastoid cell line, a concise albeit comprehensive list of O-GlcNAcylated HLA class I peptides. This cumulative list of O-GlcNAcylated HLA peptides were derived from normal and cancerous origin, as well as tissue specimen. Remarkably, the overlap in detected O-GlcNAcylated HLA peptides as well as their source proteins is strikingly high. Most of the O-GlcNAcylated HLA peptides originate from nuclear proteins, notably transcription factors. From this list, we extract that O-GlcNAcylated HLA Class I peptides are preferentially presented by the HLA-B*07:02 allele. This allele loads peptides with a Proline residue anchor at position 2, and features a binding groove that can accommodate well the recently proposed consensus sequence for O-GlcNAcylation, P(V/A/T/S)g(S/T), essentially explaining why HLA-B*07:02 is a favoured binding allele. The observations drawn from the compiled list, may assist in the prediction of novel O-GlcNAcylated HLA antigens, which will be best presented by patients harbouring HLA-B*07:02 or related alleles that use Proline as anchoring residue. Frontiers Media S.A. 2021-12-01 /pmc/articles/PMC8671986/ /pubmed/34925382 http://dx.doi.org/10.3389/fimmu.2021.796584 Text en Copyright © 2021 Mukherjee, Sanchez-Bernabeu, Demmers, Wu and Heck https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Mukherjee, Soumya Sanchez-Bernabeu, Alvaro Demmers, Laura C. Wu, Wei Heck, Albert J. R. The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title | The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title_full | The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title_fullStr | The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title_full_unstemmed | The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title_short | The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02 |
title_sort | hla ligandome comprises a limited repertoire of o-glcnacylated antigens preferentially associated with hla-b*07:02 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671986/ https://www.ncbi.nlm.nih.gov/pubmed/34925382 http://dx.doi.org/10.3389/fimmu.2021.796584 |
work_keys_str_mv | AT mukherjeesoumya thehlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT sanchezbernabeualvaro thehlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT demmerslaurac thehlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT wuwei thehlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT heckalbertjr thehlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT mukherjeesoumya hlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT sanchezbernabeualvaro hlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT demmerslaurac hlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT wuwei hlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 AT heckalbertjr hlaligandomecomprisesalimitedrepertoireofoglcnacylatedantigenspreferentiallyassociatedwithhlab0702 |