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  • Title: Negative selection of CD4+ CD8+ thymocytes by T-cell receptor peptide antagonists.
    Author: Page DM, Alexander J, Snoke K, Appella E, Sette A, Hedrick SM, Grey HM.
    Journal: Proc Natl Acad Sci U S A; 1994 Apr 26; 91(9):4057-61. PubMed ID: 7909610.
    Abstract:
    Antigen-induced activation of T cells can be specifically inhibited by antigen analogs that have been termed T-cell receptor peptide antagonists. These antagonists appear to act by inducing the formation of nonstimulatory or partially stimulatory complexes between T-cell receptors and the major histocompatibility complex molecules presenting the peptides. Herein, we have investigated the effect of T-cell receptor peptide antagonists on thymocyte negative selection. First, peptide antagonists were identified for the cytochrome c-specific T-cell clone AD10. These peptides were then tested for their ability to induce negative selection in an in vitro model system using thymocytes from mice transgenic for the AD10 T-cell receptor. Though unable to induce mature T-cell activation, the T-cell receptor peptide antagonists induced deletion of CD4+ CD8+ thymocytes. These results suggest that negative selection of CD4+ CD8+ thymocytes can be induced by T-cell receptor interactions of a lower affinity than those required for mature T-cell activation.
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