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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.
Afiliación
  • Hamze M; CEA-Saclay, Institut de Biologie et Technologies, Université Paris-Saclay, Gif sur Yvette, France.
  • Meunier S; CEA-Saclay, Institut de Biologie et Technologies, Université Paris-Saclay, Gif sur Yvette, France.
  • Karle A; Novartis Pharma AG, Basel, Switzerland.
  • Gdoura A; CEA-Saclay, Institut de Biologie et Technologies, Université Paris-Saclay, Gif sur Yvette, France.
  • Goudet A; CEA-Saclay, Institut de Biologie et Technologies, Université Paris-Saclay, Gif sur Yvette, France.
  • Szely N; INSERM UMR 996, Faculté de Pharmacie, Université Paris-Sud, Chatenay Malabry, France.
  • Pallardy M; INSERM UMR 996, Faculté de Pharmacie, Université Paris-Sud, Chatenay Malabry, France.
  • Carbonnel F; Service de gastro-entérologie, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France.
  • Spindeldreher S; Novartis Pharma AG, Basel, Switzerland.
  • Mariette X; INSERM UMR 1184, Assistance Publique-Hôpitaux de Paris, Service de Rhumatologie, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France.
  • Miceli-Richard C; INSERM UMR 1184, Assistance Publique-Hôpitaux de Paris, Service de Rhumatologie, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France.
  • Maillère B; CEA-Saclay, Institut de Biologie et Technologies, Université Paris-Saclay, Gif sur Yvette, France.
Front Immunol ; 8: 500, 2017.
Article en En | MEDLINE | ID: mdl-28529511
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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Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Immunol Año: 2017 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Immunol Año: 2017 Tipo del documento: Article