title: TCR Signal Strength and T Cell Development.
abstract: Thymocyte selection involves the positive and negative selection of the repertoire of T cell receptors (TCRs) such that the organism does not suffer autoimmunity, yet has the benefit of the ability to recognize any invading pathogen. The signal transduced through the TCR is translated into a number of different signaling cascades that result in transcription factor activity in the nucleus and changes to the cytoskeleton and motility. Negative selection involves inducing apoptosis in thymocytes that express strongly self-reactive TCRs, whereas positive selection must induce survival and differentiation programs in cells that are more weakly self-reactive. The TCR recognition event is analog by nature, but the outcome of signaling is not. A large number of molecules regulate the strength of the TCR-derived signal at various points in the cascades. This review discusses the various factors that can regulate the strength of the TCR signal during thymocyte development.
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, and Immunology Program, National University of Singapore, Singapore 11759; email: micnrjg@nus.edu.sg.
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
authors.affiliation: Laboratory of Immunobiology, REGA Institute, Department of Microbiology and Immunology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Vasily
authors.initials: V
authors.lastname: Rybakin
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Oreste
authors.initials: O
authors.lastname: Acuto
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, and Immunology Program, National University of Singapore, Singapore 11759; email: micnrjg@nus.edu.sg.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brzostek
mesh_terms: D000818:Animals; D006801:Humans; D016131:Lymphocyte Subsets / Q000378:metabolism; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D046988:Proteasome Endopeptidase Complex
keywords: T cell development; T cell receptor; Themis; signaling; thymus