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.
Baldwin
K K
KK
Program in Immunology, Department of Microbiology and Immunology, Howard Hughes Medical Institute, Stanford University, CA 94305, USA.
Trenchak
B P
BP
Altman
J D
JD
Davis
M M
MM
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