Title |
Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors
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Published in |
Frontiers in immunology, May 2017
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DOI | 10.3389/fimmu.2017.00500 |
Pubmed ID | |
Authors |
Moustafa Hamze, Sylvain Meunier, Anette Karle, Abdelaziz Gdoura, Amélie Goudet, Natacha Szely, Marc Pallardy, Franck Carbonnel, Sebastian Spindeldreher, Xavier Mariette, Corinne Miceli-Richard, Bernard 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 DCs to anticipate and prevent immunogenicity of therapeutic antibodies. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 29% |
United Kingdom | 2 | 29% |
Switzerland | 1 | 14% |
Unknown | 2 | 29% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 3 | 43% |
Members of the public | 3 | 43% |
Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 65 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 19 | 29% |
Student > Ph. D. Student | 9 | 14% |
Student > Bachelor | 4 | 6% |
Librarian | 3 | 5% |
Student > Doctoral Student | 2 | 3% |
Other | 7 | 11% |
Unknown | 21 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 12 | 18% |
Agricultural and Biological Sciences | 9 | 14% |
Biochemistry, Genetics and Molecular Biology | 7 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 8% |
Medicine and Dentistry | 5 | 8% |
Other | 7 | 11% |
Unknown | 20 | 31% |