Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Characterization of CD4 T cell epitopes of infliximab and rituximab identified from healthy donors

Hamze, Moustafa and Meunier, Sylvain and Karle, Anette and Gdoura, Abdelaziz and Goudet, Amelie and Szely, Natacha and Pallardy, Marc and Carbonnel, Franck and Spindeldreher, Sebastian and Mariette, Xavier and 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

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.