Negative selection of T cells occurs throughout thymic development.
Thymic positive and negative selections govern the development of a self-MHC-reactive, yet self-tolerant, T cell repertoire. Whether these processes occur independently or sequentially remains controversial. To investigate these issues, we have employed tetrameric peptide-MHC complexes to fluorescently label and monitor polyclonal populations of thymocytes that are specific for moth cytochrome c (MCC)/I-Ek. In TCR beta mice tetramer-positive thymocytes are detectable even in the most immature TCR-expressing cells. In the presence of MCC peptide, thymocytes that bind strongly to MCC/I-Ek tetramers are deleted earlier in development and more extensively than cells that bind weakly. This negative selection of the MCC/I-Ek-specific cells occurs continuously throughout development and before any evidence of positive selection. Thus, positive and negative selections are independent processes that need not occur sequentially.
Program in Immunology, Department of Microbiology and Immunology, Howard Hughes Medical Institute, Stanford University, CA 94305, USA.
K K
KK
Baldwin
B P
BP
Trenchak
J D
JD
Altman
M M
MM
Davis
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D003574:Cytochrome c Group / Q000096:biosynthesis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology*; D013997:Time Factors
D003574:Cytochrome c Group; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell