CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate

Shaomin Tian, Robert Maile, Edward J. Collins, Jeffrey A Frelinger

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC Db. pMHC binding, TCR-binding characteristics, CD8+ T cell cytotoxicity, and IFN-γ production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-γ production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-γ production. This study strongly argues for an affinity threshold model of T cell activation.

Original languageEnglish (US)
Pages (from-to)2952-2960
Number of pages9
JournalJournal of Immunology
Volume179
Issue number5
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

T-Lymphocytes
Peptides
Lymphocytic choriomeningitis virus
Biochemistry
Epitopes
Ligands
MHC binding peptide

ASJC Scopus subject areas

  • Immunology

Cite this

CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate. / Tian, Shaomin; Maile, Robert; Collins, Edward J.; Frelinger, Jeffrey A.

In: Journal of Immunology, Vol. 179, No. 5, 01.09.2007, p. 2952-2960.

Research output: Contribution to journalArticle

Tian, Shaomin ; Maile, Robert ; Collins, Edward J. ; Frelinger, Jeffrey A. / CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate. In: Journal of Immunology. 2007 ; Vol. 179, No. 5. pp. 2952-2960.
@article{7f1627f178ae48928c02adc539e0f4a8,
title = "CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate",
abstract = "Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC Db. pMHC binding, TCR-binding characteristics, CD8+ T cell cytotoxicity, and IFN-γ production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-γ production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-γ production. This study strongly argues for an affinity threshold model of T cell activation.",
author = "Shaomin Tian and Robert Maile and Collins, {Edward J.} and Frelinger, {Jeffrey A}",
year = "2007",
month = "9",
day = "1",
language = "English (US)",
volume = "179",
pages = "2952--2960",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate

AU - Tian, Shaomin

AU - Maile, Robert

AU - Collins, Edward J.

AU - Frelinger, Jeffrey A

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC Db. pMHC binding, TCR-binding characteristics, CD8+ T cell cytotoxicity, and IFN-γ production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-γ production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-γ production. This study strongly argues for an affinity threshold model of T cell activation.

AB - Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC Db. pMHC binding, TCR-binding characteristics, CD8+ T cell cytotoxicity, and IFN-γ production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-γ production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-γ production. This study strongly argues for an affinity threshold model of T cell activation.

UR - http://www.scopus.com/inward/record.url?scp=38449086723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38449086723&partnerID=8YFLogxK

M3 - Article

VL - 179

SP - 2952

EP - 2960

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -