A kinetic threshold between negative and positive selection based on the longevity of the T cell receptor-ligand complex

Calvin B. Williams, Deborah L. Engle, Gilbert J. Kersh, J. Michael White, Paul M. Allen

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96 Scopus citations

Abstract

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II-restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64-76)/I-E(k) and positively selected on I-E(k) plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR-ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR-ligand complexes.

Original languageEnglish
Pages (from-to)1531-1544
Number of pages14
JournalJournal of Experimental Medicine
Volume189
Issue number10
DOIs
StatePublished - May 17 1999

Keywords

  • Altered peptide ligand
  • Selection
  • T cell receptor
  • Thymocyte
  • Transgenic

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