Preselection thymocytes are more sensitive to T cell receptor stimulation than mature T cells

Gayle M. Davey, Sonya L. Schober, Bart T. Endrizzi, Angela K. Dutcher, Stephen C. Jameson, Kristin A. Hogquist

Research output: Contribution to journalArticle

164 Scopus citations

Abstract

During T cell development, thymocytes which are tolerant to self- peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide-major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self- peptide-MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide-MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide-MHC complexes.

Original languageEnglish (US)
Pages (from-to)1867-1874
Number of pages8
JournalJournal of Experimental Medicine
Volume188
Issue number10
DOIs
StatePublished - Nov 16 1998

Keywords

  • Calcium signaling
  • Lymphocyte development
  • T cell receptor
  • Thymus

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