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 language | English (US) |
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Pages (from-to) | 7639-7643 |
Number of pages | 5 |
Journal | Journal of Immunology |
Volume | 183 |
Issue number | 12 |
DOIs | |
State | Published - Dec 15 2009 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology