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Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients

Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4(+) T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are larg...

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Autores principales: Milcent, Benoit, Josseaume, Nathalie, Riller, Quentin, Giglioli, Ilenia, Rabia, Emilia, Deligne, Claire, Latouche, Jean-Baptiste, Hamieh, Mohamad, Couture, Alexandre, Toutirais, Olivier, Lone, Yu-Chun, Jeger-Madiot, Raphaël, Graff-Dubois, Stéphanie, Amorim, Sandy, Loiseau, Pascale, Toubert, Antoine, Brice, Pauline, Thieblemont, Catherine, Teillaud, Jean-Luc, Sibéril, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805815/
https://www.ncbi.nlm.nih.gov/pubmed/31494742
http://dx.doi.org/10.1007/s00262-019-02389-7
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author Milcent, Benoit
Josseaume, Nathalie
Riller, Quentin
Giglioli, Ilenia
Rabia, Emilia
Deligne, Claire
Latouche, Jean-Baptiste
Hamieh, Mohamad
Couture, Alexandre
Toutirais, Olivier
Lone, Yu-Chun
Jeger-Madiot, Raphaël
Graff-Dubois, Stéphanie
Amorim, Sandy
Loiseau, Pascale
Toubert, Antoine
Brice, Pauline
Thieblemont, Catherine
Teillaud, Jean-Luc
Sibéril, Sophie
author_facet Milcent, Benoit
Josseaume, Nathalie
Riller, Quentin
Giglioli, Ilenia
Rabia, Emilia
Deligne, Claire
Latouche, Jean-Baptiste
Hamieh, Mohamad
Couture, Alexandre
Toutirais, Olivier
Lone, Yu-Chun
Jeger-Madiot, Raphaël
Graff-Dubois, Stéphanie
Amorim, Sandy
Loiseau, Pascale
Toubert, Antoine
Brice, Pauline
Thieblemont, Catherine
Teillaud, Jean-Luc
Sibéril, Sophie
author_sort Milcent, Benoit
collection PubMed
description Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4(+) T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2(+)-DR1(+) transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02389-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-68058152019-11-05 Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients Milcent, Benoit Josseaume, Nathalie Riller, Quentin Giglioli, Ilenia Rabia, Emilia Deligne, Claire Latouche, Jean-Baptiste Hamieh, Mohamad Couture, Alexandre Toutirais, Olivier Lone, Yu-Chun Jeger-Madiot, Raphaël Graff-Dubois, Stéphanie Amorim, Sandy Loiseau, Pascale Toubert, Antoine Brice, Pauline Thieblemont, Catherine Teillaud, Jean-Luc Sibéril, Sophie Cancer Immunol Immunother Original Article Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4(+) T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2(+)-DR1(+) transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02389-7) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-09-07 2019 /pmc/articles/PMC6805815/ /pubmed/31494742 http://dx.doi.org/10.1007/s00262-019-02389-7 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Milcent, Benoit
Josseaume, Nathalie
Riller, Quentin
Giglioli, Ilenia
Rabia, Emilia
Deligne, Claire
Latouche, Jean-Baptiste
Hamieh, Mohamad
Couture, Alexandre
Toutirais, Olivier
Lone, Yu-Chun
Jeger-Madiot, Raphaël
Graff-Dubois, Stéphanie
Amorim, Sandy
Loiseau, Pascale
Toubert, Antoine
Brice, Pauline
Thieblemont, Catherine
Teillaud, Jean-Luc
Sibéril, Sophie
Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title_full Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title_fullStr Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title_full_unstemmed Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title_short Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients
title_sort presence of t cells directed against cd20-derived peptides in healthy individuals and lymphoma patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805815/
https://www.ncbi.nlm.nih.gov/pubmed/31494742
http://dx.doi.org/10.1007/s00262-019-02389-7
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