title: Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling.
abstract: Signaling via the T cell antigen receptor (TCR) during the CD4(+)CD8(+) double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell-expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1(-/-) mice had fewer mature thymic CD4(+) and CD8(+) T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-γ1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca(2+)-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zheng
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Yao
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Qiu
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Lou
authors.forename: Chuan
authors.initials: C
authors.lastname: Ouyang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuewei
authors.initials: Y
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Chi
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D003001:Cloning, Molecular; D051380:GRB2 Adaptor Protein / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma / Q000276:immunology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C574974:Tespa1 protein, mouse; D051966:Phospholipase C gamma