Positive selection of CD4+ t cells is induced in vivo by agonist and inhibited by antagonist peptides

P. Kraj, R. Pacholczyk, H. Ignatowicz, P. Kisielow, P. Jensen, L. Ignatowicz

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.

Original languageEnglish (US)
Pages (from-to)407-416
Number of pages10
JournalJournal of Experimental Medicine
Volume194
Issue number4
DOIs
StatePublished - Aug 20 2001

Keywords

  • Agonist peptide
  • CD4 cells
  • MHC class II
  • Positive selection
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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