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© Research
Publication : Frontiers in immunology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Frontiers in immunology - 05 May 2017

Hamze M, Meunier S, Karle A, Gdoura A, Goudet A, Szely N, Pallardy M, Carbonnel F, Spindeldreher S, Mariette X, Miceli-Richard C, Maillère B

Link to Pubmed [PMID] – 28529511

Front Immunol 2017;8:500

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.

https://www.ncbi.nlm.nih.gov/pubmed/28529511