Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life.

Détails

ID Serval
serval:BIB_8C526C41A0DD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Rubio-Godoy V., Dutoit V., Rimoldi D., Lienard D., Lejeune F., Speiser D., Guillaume P., Cerottini J.C., Romero P., Valmori D.
ISSN
0027-8424
Statut éditorial
Publié
Date de publication
08/2001
Peer-reviewed
Oui
Volume
98
Numéro
18
Pages
10302-10307
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article - Publication Status: ppublish
Résumé
Activation of CD8(+) cytolytic T lymphocytes (CTLs) by antigen is triggered by the interaction of clonotypic alphabeta T cell receptors (TCRs) with antigenic peptides bound to MHC class I molecules (pMHC complexes). Fluorescent multimeric pMHC complexes have been shown to specifically stain antigen-specific CTLs by directly binding the TCR. In tumor-infiltrating lymphocytes from a melanoma patient we found a high frequency of tyrosinase(368-376) peptide-specific cells as detected by IFN-gamma ELISPOT, without detectable staining with the corresponding A2/peptide multimers. Surprisingly, these T cells were able to lyse tyrosinase(368-376) peptide-pulsed target cells as efficiently as other specific T cells that were stained by multimers. Analysis of the staining patterns under different conditions of incubation time and temperature revealed that these results were explained by major differences in TCR-multimeric ligand interaction kinetics among the clones. Whereas no direct quantitative correlation between antigenic peptide concentration required for CTL effector functions and equilibrium multimer binding was observed interclonally, the latter was profoundly affected by the kinetics of TCR-ligand interaction. More importantly, our data indicate that similar levels of T cell activation can be achieved by independent CD8(+) T cell clonotypes displaying different TCR/pMHC complex dissociation rates.
Mots-clé
Clone Cells, Enzyme-Linked Immunosorbent Assay, HLA-A2 Antigen/chemistry, HLA-A2 Antigen/metabolism, Half-Life, Humans, Interferon-gamma/secretion, Kinetics, Ligands, Lymphocytes, Tumor-Infiltrating/immunology, Macromolecular Substances, Melanoma/immunology, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/metabolism, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:14
Dernière modification de la notice
08/05/2019 21:45
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