Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783461481802629120 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6805815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT milcentbenoit presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT josseaumenathalie presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT rillerquentin presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT giglioliilenia presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT rabiaemilia presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT deligneclaire presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT latouchejeanbaptiste presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT hamiehmohamad presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT couturealexandre presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT toutiraisolivier presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT loneyuchun presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT jegermadiotraphael presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT graffduboisstephanie presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT amorimsandy presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT loiseaupascale presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT toubertantoine presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT bricepauline presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT thieblemontcatherine presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT teillaudjeanluc presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients AT siberilsophie presenceoftcellsdirectedagainstcd20derivedpeptidesinhealthyindividualsandlymphomapatients |