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Publication : Double-positive T cell receptor(high) thymocytes are resistant to peptide/major histocompatibility complex ligand-induced negative selection.

First Author  Ghendler Y Year  1997
Journal  Eur J Immunol Volume  27
Issue  9 Pages  2279-89
PubMed ID  9341770 Mgi Jnum  J:133112
Mgi Id  MGI:3777739 Doi  10.1002/eji.1830270923
Citation  Ghendler Y, et al. (1997) Double-positive T cell receptor(high) thymocytes are resistant to peptide/major histocompatibility complex ligand-induced negative selection. Eur J Immunol 27(9):2279-89
abstractText  To investigate negative selection events during intrathymic ontogeny, we established T cell receptor (TCR)-transgenic mice [N15tg/RAG-2-/- (H-2b)] expressing a single TCR specific for vesicular stomatitis virus nuclear octapeptide N52-59 (VSV8) in the context of the major histocompatibility complex (MHC) class I molecule, K(b). Administration of VSV8 in vivo induced apoptosis in less than 4 h, deleting the majority of immature double-positive (DP) thymocytes by 24 h. In contrast, DP TCRhigh as well as single-positive (SP) thymocytes were refractory to this death process. Moreover, DP TCRhigh cells differentiated into SP thymocytes in vitro and in vivo, maturing into functional cytotoxic T lymphocytes upon intrathymic transfer to beta RAG 2-/- recipients. Hence, negative selection processes involving MHC-bound peptide ligands are operative only prior to the late DP thymocyte stage in this MHC class I-restricted TCR transgene system.
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