PMID- 28529511
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified 
      from Healthy Donors.
PG  - 500
LID - 10.3389/fimmu.2017.00500 [doi]
LID - 500
AB  - The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFalpha 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.
FAU - Hamze, Moustafa
AU  - Hamze M
AD  - CEA-Saclay, Institut de Biologie et Technologies, Universite Paris-Saclay, Gif 
      sur Yvette, France.
FAU - Meunier, Sylvain
AU  - Meunier S
AD  - CEA-Saclay, Institut de Biologie et Technologies, Universite Paris-Saclay, Gif 
      sur Yvette, France.
FAU - Karle, Anette
AU  - Karle A
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Gdoura, Abdelaziz
AU  - Gdoura A
AD  - CEA-Saclay, Institut de Biologie et Technologies, Universite Paris-Saclay, Gif 
      sur Yvette, France.
FAU - Goudet, Amelie
AU  - Goudet A
AD  - CEA-Saclay, Institut de Biologie et Technologies, Universite Paris-Saclay, Gif 
      sur Yvette, France.
FAU - Szely, Natacha
AU  - Szely N
AD  - INSERM UMR 996, Faculte de Pharmacie, Universite Paris-Sud, Chatenay Malabry, 
      France.
FAU - Pallardy, Marc
AU  - Pallardy M
AD  - INSERM UMR 996, Faculte de Pharmacie, Universite Paris-Sud, Chatenay Malabry, 
      France.
FAU - Carbonnel, Franck
AU  - Carbonnel F
AD  - Service de gastro-enterologie, Hopitaux Universitaires Paris-Sud, Le 
      Kremlin-Bicetre, France.
FAU - Spindeldreher, Sebastian
AU  - Spindeldreher S
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Mariette, Xavier
AU  - Mariette X
AD  - INSERM UMR 1184, Assistance Publique-Hopitaux de Paris, Service de Rhumatologie, 
      Hopitaux Universitaires Paris-Sud, Universite Paris-Sud, Le Kremlin-Bicetre, 
      France.
FAU - Miceli-Richard, Corinne
AU  - Miceli-Richard C
AD  - INSERM UMR 1184, Assistance Publique-Hopitaux de Paris, Service de Rhumatologie, 
      Hopitaux Universitaires Paris-Sud, Universite Paris-Sud, Le Kremlin-Bicetre, 
      France.
FAU - Maillere, Bernard
AU  - Maillere B
AD  - CEA-Saclay, Institut de Biologie et Technologies, Universite Paris-Saclay, Gif 
      sur Yvette, France.
LA  - eng
PT  - Journal Article
DEP - 20170505
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5418239
OTO - NOTNLM
OT  - CD4 T cell epitopes
OT  - MHC-associated peptide proteomics
OT  - antidrug antibody
OT  - healthy donors
OT  - immunogenicity
OT  - infliximab
OT  - rituximab
OT  - therapeutic antibodies
EDAT- 2017/05/23 06:00
MHDA- 2017/05/23 06:01
PMCR- 2017/01/01
CRDT- 2017/05/23 06:00
PHST- 2017/02/12 00:00 [received]
PHST- 2017/04/11 00:00 [accepted]
PHST- 2017/05/23 06:00 [entrez]
PHST- 2017/05/23 06:00 [pubmed]
PHST- 2017/05/23 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.00500 [doi]
PST - epublish
SO  - Front Immunol. 2017 May 5;8:500. doi: 10.3389/fimmu.2017.00500. eCollection 2017.