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  • Title: Cutting edge: inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands.
    Author: Chervin AS, Stone JD, Bowerman NA, Kranz DM.
    Journal: J Immunol; 2009 Dec 15; 183(12):7639-43. PubMed ID: 19923452.
    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 cross-reactivities 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 (K(D) = 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.
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