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

Frontiers in Immunology
Moustafa HamzeBernard Maillère

Abstract

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 DC...Continue Reading

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Citations

Feb 3, 2018·Dermatology and Therapy·Sebastian SpindeldreherFrank Kolbinger
Jun 19, 2019·Bioanalysis·Sophie Tourdot, Timothy P Hickling
Oct 30, 2019·Cellular & Molecular Immunology·Sylvain MeunierBernard Maillère
Jul 30, 2020·Protein Engineering, Design & Selection : PEDS·Marcia SticklerFiona A Harding
May 19, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aurélien AzamBernard Maillère
Oct 2, 2019·International Journal of Molecular Sciences·Rune Alexander HøglundTrygve Holmøy
Aug 15, 2020·Frontiers in Immunology·Sylvain MeunierBernard Maillère
May 7, 2020·Frontiers in Immunology·Anette C Karle
Jan 12, 2020·MAbs·Sebastian SpindeldreherFrank Kolbinger
Nov 23, 2020·Cell Reports·Michael D KniermanRobert W Siegel
Dec 16, 2020·Nature Reviews. Rheumatology·Vibeke StrandJohn D Isaacs
Apr 5, 2021·Journal of Pharmaceutical Sciences·Katharine Bray-FrenchAxel Ducret

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Methods Mentioned

BETA
immunoprecipitation
ELISA
proteomics assay

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