CD8-T cell transfectants that express a high affinity T cell receptor exhibit enhanced peptide-dependent activation

P. D. Holler, A. R. Lim, B. K. Cho, L. A. Rund, D. M. Kranz

Research output: Contribution to journalArticle

Abstract

T cells are activated by binding of the T cell receptor (TCR) to a peptide-major histocompatibility complex (MHC) complex (pMHC) expressed on the surface of antigen presenting cells. Various models have predicted that activation is limited to a narrow window of affinities (or dissociation rates) for the TCI-pMHC interaction and that above or below this window, T cells will fail to undergo activation. However, to date there have not been TCRs with sufficiently high affinities in order to test this hypothesis. In this report we examined the activity of a CD8-negative T cell line transfected with a high affinity mutant TCR (KD = 10 nM) derived from cytotoxic T lymphocyte clone 2C by in vitro engineering. The results show that despite a 300-fold higher affinity and a 45-fold longer off-rate compared with the wild-type TCR, T cells that expressed the mutant TCRs were activated by peptide. In fact, activation could be detected at significantly lower peptide concentrations than with T cells that expressed the wildtype TCI. Furthermore, binding and functional analyses of a panel of peptide variants suggested that pMHC stability could account for apparent discrepancies between TCR affinity and T cell activity observed in several prior studies.

Original languageEnglish (US)
Pages (from-to)1043-1052
Number of pages10
JournalJournal of Experimental Medicine
Volume194
Issue number8
DOIs
StatePublished - Oct 15 2001

Keywords

  • Binding affinity
  • Dissociation rate
  • Interleukin 2
  • T cell activity
  • Yeast surface display

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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