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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / immunology
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Differentiation / immunology
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Cloning, Molecular
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GRB2 Adaptor Protein / immunology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Phospholipase C gamma / immunology
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RNA, Messenger / chemistry
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RNA, Messenger / genetics
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Receptors, Antigen, T-Cell / immunology*
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Signal Transduction / immunology
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T-Lymphocytes / immunology*
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Thymus Gland / cytology
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Thymus Gland / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Tespa1 protein, mouse
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Phospholipase C gamma