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...

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Autores principales:	Soumya Mukherjee, Alvaro Sanchez-Bernabeu, Laura C. Demmers, Wei Wu, Albert J. R. Heck
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	O-GlcNAcylation modification HLA MHC immunopeptidome HLA-B*07:02 neo-antigen Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/315635dc04194cb58580603d123a433a
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spelling	oai:doaj.org-article:315635dc04194cb58580603d123a433a2021-12-01T23:54:35ZThe HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B07:021664-322410.3389/fimmu.2021.796584https://doaj.org/article/315635dc04194cb58580603d123a433a2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.796584/fullhttps://doaj.org/toc/1664-3224Mass-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-B07:02 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-B07:02 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-B07:02 or related alleles that use Proline as anchoring residue.Soumya MukherjeeSoumya MukherjeeAlvaro Sanchez-BernabeuAlvaro Sanchez-BernabeuLaura C. DemmersLaura C. DemmersWei WuWei WuAlbert J. R. HeckAlbert J. R. HeckFrontiers Media S.A.articleO-GlcNAcylation modificationHLAMHCimmunopeptidomeHLA-B*07:02neo-antigenImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	O-GlcNAcylation modification HLA MHC immunopeptidome HLA-B*07:02 neo-antigen Immunologic diseases. Allergy RC581-607
spellingShingle	O-GlcNAcylation modification HLA MHC immunopeptidome HLA-B07:02 neo-antigen Immunologic diseases. Allergy RC581-607 Soumya Mukherjee Soumya Mukherjee Alvaro Sanchez-Bernabeu Alvaro Sanchez-Bernabeu Laura C. Demmers Laura C. Demmers Wei Wu Wei Wu Albert J. R. Heck Albert J. R. Heck The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B07:02
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-B07:02 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-B07:02 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	article
author	Soumya Mukherjee Soumya Mukherjee Alvaro Sanchez-Bernabeu Alvaro Sanchez-Bernabeu Laura C. Demmers Laura C. Demmers Wei Wu Wei Wu Albert J. R. Heck Albert J. R. Heck
author_facet	Soumya Mukherjee Soumya Mukherjee Alvaro Sanchez-Bernabeu Alvaro Sanchez-Bernabeu Laura C. Demmers Laura C. Demmers Wei Wu Wei Wu Albert J. R. Heck Albert J. R. Heck
author_sort	Soumya Mukherjee
title	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_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_sort	hla ligandome comprises a limited repertoire of o-glcnacylated antigens preferentially associated with hla-b*07:02
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/315635dc04194cb58580603d123a433a
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The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02

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