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 journalArticlepeer-review

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

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