Hamze, Moustafa, Meunier, Sylvain, Karle, Anette, Gdoura, Abdelaziz, Goudet, Amelie, Szely, Natacha, Pallardy, Marc, Carbonnel, Franck, Spindeldreher, Sebastian, Mariette, Xavier, Miceli-Richard, Corinne and Maillere, Bernard (2017) Characterization of CD4 T cell epitopes of infliximab and rituximab identified from healthy donors. Frontiers in immunology, 8 (MAY). pp. 1-11. ISSN 1664-3224

Abstract

The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFa 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.

Item Type:	Article
Keywords:	Antidrug antibody CD4 T cell epitopes Healthy donors Immunogenicity Infliximab MHC-associated peptide proteomics Rituximab Therapeutic antibodies
Date Deposited:	06 Apr 2018 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/33097