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- Title
T-cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection.
- Authors
Clayton, L K; Ghendler, Y; Mizoguchi, E; Patch, R J; Ocain, T D; Orth, K; Bhan, A K; Dixit, V M; Reinherz, E L
- Abstract
T-cell receptors (TCRs) are created by a stochastic gene rearrangement process during thymocyte development, generating thymocytes bearing useful, as well as unwanted, specificities. Within the latter group, autoreactive thymocytes arise which are subsequently eliminated via a thymocyte-specific apoptotic mechanism, termed negative selection. The molecular basis of this deletion is unknown. Here, we show that TCR triggering by peptide/MHC ligands activates a caspase in double-positive (DP) CD4+ CD8+ thymocytes, resulting in their death. Inhibition of this enzymatic activity prevents antigen-induced death of DP thymocytes in fetal thymic organ culture (FTOC) from TCR transgenic mice as well as apoptosis induced by anti-CD3epsilon monoclonal antibody and corticosteroids in FTOC of normal C57BL/6 mice. Hence, a common caspase mediates immature thymocyte susceptibility to cell death.
- Publication
The EMBO journal, 1997, Vol 16, Issue 9, p2282
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/16.9.2282