TCR-ligand dissociation rate is a robust and stable biomarker of CD8+ T cell potency.

Détails

Ressource 1Télécharger: 5_28724801_Postprint.pdf (8226.80 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_336570E7506E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TCR-ligand dissociation rate is a robust and stable biomarker of CD8+ T cell potency.
Périodique
JCI insight
Auteur(s)
Allard M., Couturaud B., Carretero-Iglesia L., Duong M.N., Schmidt J., Monnot G.C., Romero P., Speiser D.E., Hebeisen M., Rufer N.
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Statut éditorial
Publié
Date de publication
20/07/2017
Peer-reviewed
Oui
Volume
2
Numéro
14
Pages
e92570
Langue
anglais
Notes
Publication types: Journal Article

Résumé
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors. We demonstrate that monomeric TCR-pMHC dissociation rates accurately predict the extent of cytotoxicity, cytokine production, polyfunctionality, cell proliferation, activating/inhibitory receptor expression, and in vivo antitumor potency of naturally occurring antigen-specific CD8+ T cells. Our data also confirm the superior binding avidities of virus-specific T cells as compared with self/tumor-specific T cell clonotypes (n > 300). Importantly, the TCR-pMHC off-rate is a more stable and robust biomarker of CD8+ T cell potency than the frequently used functional assays/metrics that depend on the T cell's activation state, and therefore show major intra- and interexperimental variability. Taken together, our data show that the monomeric TCR-pMHC off-rate is highly useful for the ex vivo high-throughput functional assessment of antigen-specific CD8+ T cell responses and a strong candidate as a biomarker of T cell therapeutic efficacy.

Pubmed
Web of science
Open Access
Oui
Création de la notice
04/09/2017 10:14
Dernière modification de la notice
20/08/2019 13:19
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