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Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins

The human leukocyte antigen (HLA) proteins are an indispensable component of adaptive immunity because of their role in presenting self and foreign peptides to T cells. Further, many complex diseases are associated with genetic variation in the HLA region, implying an important role for specific HLA...

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Autores principales: ElAbd, Hesham, Bacher, Petra, Tholey, Andreas, Lenz, Tobias L., Franke, Andre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090296/
https://www.ncbi.nlm.nih.gov/pubmed/37063883
http://dx.doi.org/10.3389/fimmu.2023.1107266
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author ElAbd, Hesham
Bacher, Petra
Tholey, Andreas
Lenz, Tobias L.
Franke, Andre
author_facet ElAbd, Hesham
Bacher, Petra
Tholey, Andreas
Lenz, Tobias L.
Franke, Andre
author_sort ElAbd, Hesham
collection PubMed
description The human leukocyte antigen (HLA) proteins are an indispensable component of adaptive immunity because of their role in presenting self and foreign peptides to T cells. Further, many complex diseases are associated with genetic variation in the HLA region, implying an important role for specific HLA-presented peptides in the etiology of these diseases. Identifying the specific set of peptides presented by an individual’s HLA proteins in vivo, as a whole being referred to as the immunopeptidome, has therefore gathered increasing attention for different reasons. For example, identifying neoepitopes for cancer immunotherapy, vaccine development against infectious pathogens, or elucidating the role of HLA in autoimmunity. Despite the tremendous progress made during the last decade in these areas, several questions remain unanswered. In this perspective, we highlight five remaining key challenges in the analysis of peptide presentation and T cell immunogenicity and discuss potential solutions to these problems. We believe that addressing these questions would not only improve our understanding of disease etiology but will also have a direct translational impact in terms of engineering better vaccines and in developing more potent immunotherapies.
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spelling pubmed-100902962023-04-13 Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins ElAbd, Hesham Bacher, Petra Tholey, Andreas Lenz, Tobias L. Franke, Andre Front Immunol Immunology The human leukocyte antigen (HLA) proteins are an indispensable component of adaptive immunity because of their role in presenting self and foreign peptides to T cells. Further, many complex diseases are associated with genetic variation in the HLA region, implying an important role for specific HLA-presented peptides in the etiology of these diseases. Identifying the specific set of peptides presented by an individual’s HLA proteins in vivo, as a whole being referred to as the immunopeptidome, has therefore gathered increasing attention for different reasons. For example, identifying neoepitopes for cancer immunotherapy, vaccine development against infectious pathogens, or elucidating the role of HLA in autoimmunity. Despite the tremendous progress made during the last decade in these areas, several questions remain unanswered. In this perspective, we highlight five remaining key challenges in the analysis of peptide presentation and T cell immunogenicity and discuss potential solutions to these problems. We believe that addressing these questions would not only improve our understanding of disease etiology but will also have a direct translational impact in terms of engineering better vaccines and in developing more potent immunotherapies. Frontiers Media S.A. 2023-03-29 /pmc/articles/PMC10090296/ /pubmed/37063883 http://dx.doi.org/10.3389/fimmu.2023.1107266 Text en Copyright © 2023 ElAbd, Bacher, Tholey, Lenz and Franke 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
ElAbd, Hesham
Bacher, Petra
Tholey, Andreas
Lenz, Tobias L.
Franke, Andre
Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title_full Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title_fullStr Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title_full_unstemmed Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title_short Challenges and opportunities in analyzing and modeling peptide presentation by HLA-II proteins
title_sort challenges and opportunities in analyzing and modeling peptide presentation by hla-ii proteins
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090296/
https://www.ncbi.nlm.nih.gov/pubmed/37063883
http://dx.doi.org/10.3389/fimmu.2023.1107266
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