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Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. W...

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Autores principales: Hamze, Moustafa, Meunier, Sylvain, Karle, Anette, Gdoura, Abdelaziz, Goudet, Amélie, Szely, Natacha, Pallardy, Marc, Carbonnel, Franck, Spindeldreher, Sebastian, Mariette, Xavier, Miceli-Richard, Corinne, Maillère, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418239/
https://www.ncbi.nlm.nih.gov/pubmed/28529511
http://dx.doi.org/10.3389/fimmu.2017.00500
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author Hamze, Moustafa
Meunier, Sylvain
Karle, Anette
Gdoura, Abdelaziz
Goudet, Amélie
Szely, Natacha
Pallardy, Marc
Carbonnel, Franck
Spindeldreher, Sebastian
Mariette, Xavier
Miceli-Richard, Corinne
Maillère, Bernard
author_facet Hamze, Moustafa
Meunier, Sylvain
Karle, Anette
Gdoura, Abdelaziz
Goudet, Amélie
Szely, Natacha
Pallardy, Marc
Carbonnel, Franck
Spindeldreher, Sebastian
Mariette, Xavier
Miceli-Richard, Corinne
Maillère, Bernard
author_sort Hamze, Moustafa
collection PubMed
description The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA)-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs) loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.
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spelling pubmed-54182392017-05-19 Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors Hamze, Moustafa Meunier, Sylvain Karle, Anette Gdoura, Abdelaziz Goudet, Amélie Szely, Natacha Pallardy, Marc Carbonnel, Franck Spindeldreher, Sebastian Mariette, Xavier Miceli-Richard, Corinne Maillère, Bernard Front Immunol Immunology The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA)-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs) loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies. Frontiers Media S.A. 2017-05-05 /pmc/articles/PMC5418239/ /pubmed/28529511 http://dx.doi.org/10.3389/fimmu.2017.00500 Text en Copyright © 2017 Hamze, Meunier, Karle, Gdoura, Goudet, Szely, Pallardy, Carbonnel, Spindeldreher, Mariette, Miceli-Richard and Maillère. http://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) or licensor 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
Hamze, Moustafa
Meunier, Sylvain
Karle, Anette
Gdoura, Abdelaziz
Goudet, Amélie
Szely, Natacha
Pallardy, Marc
Carbonnel, Franck
Spindeldreher, Sebastian
Mariette, Xavier
Miceli-Richard, Corinne
Maillère, Bernard
Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title_full Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title_fullStr Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title_full_unstemmed Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title_short Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
title_sort characterization of cd4 t cell epitopes of infliximab and rituximab identified from healthy donors
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418239/
https://www.ncbi.nlm.nih.gov/pubmed/28529511
http://dx.doi.org/10.3389/fimmu.2017.00500
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