Negative selection of CD4+ CD8+ thymocytes by T-cell receptor peptide antagonists.
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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Department of Biology, University of California at San Diego, La Jolla 92093-0063.
Alexander
J
J
Snoke
K
K
Appella
E
E
Sette
A
A
Hedrick
S M
SM
Grey
H M
HM
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D017637:Clonal Deletion; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell