Cutting edge: Inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands

Adam S. Chervin, Jennifer D. Stone, Natalie A. Bowerman, David M. Kranz

Research output: Contribution to journalArticle

Abstract

It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand crossreactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD=17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as "coreceptor inhibitors" to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.

Original languageEnglish (US)
Pages (from-to)7639-7643
Number of pages5
JournalJournal of Immunology
Volume183
Issue number12
DOIs
StatePublished - Dec 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Cutting edge: Inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands'. Together they form a unique fingerprint.

  • Cite this