title: Fine-tuning T cell receptor signaling to control T cell development.
abstract: T cell development from immature CD4(+)CD8(+) double-positive (DP) thymocytes to the mature CD4 or CD8 single-positive (SP) stage requires proper T cell receptor (TCR) signaling. The current working model of thymocyte development is that the strength of the TCR-mediated signal - from little-or-none, through intermediate, to strong - received by the immature cells determines whether they will undergo death by neglect, positive selection, or negative selection, respectively. In recent years, several developmentally regulated, stage-specifically expressed proteins and miRNAs have been found that act like fine-tuners for signal transduction and propagation downstream of the TCR. This allows them to govern thymocyte positive selection. Here, we summarize recent findings on these molecules and suggest new concepts of TCR positive-selection signaling.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597.
authors.forename: Vasily
authors.initials: V
authors.lastname: Rybakin
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brzostek
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Paster
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Oreste
authors.initials: O
authors.lastname: Acuto
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597. Electronic address: micnrjg@nus.edu.sg.
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002454:Cell Differentiation; D060966:Clonal Selection, Antigen-Mediated; D005326:Fetal Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*
chemical_list: D005326:Fetal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D011948:Receptors, Antigen, T-Cell; C557796:thymocyte-expressed molecule involved in selection, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: T cell development; Tespa1; Themis; miR-181; signaling; thymocyte; voltage-gated sodium channel