Abstract:
: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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Ghendler Y,Hussey RE,Witte T,Mizoguchi E,Clayton LK,Bhan AK,Koyasu S,Chang HC,Reinherz ELdoi
10.1002/eji.1830270923subject
Has Abstractpub_date
1997-09-01 00:00:00pages
2279-89issue
9eissn
0014-2980issn
1521-4141journal_volume
27pub_type
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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abstract::Human Vgamma9Vdelta2 T cells contribute to immunity against intracellular pathogens and recognize nonpeptidic antigens, such as the mycobacterial phosphoantigen TUBAg. HIV infection is associated with a polyclonal decrease of peripheral Vgamma9Vdelta2 T cells and we previously reported that the remaining cells show a ...
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