Journal
NATURE IMMUNOLOGY
Volume 13, Issue 6, Pages 560-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2301
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Funding
- National Natural Science Foundation of China [30972724, 31070782, 30901311, 31170842]
- Zhejiang Provincial Natural Science Foundation of China [R2090202, Y2090401]
- National Basic Research Program of China (973 Program) [2011CB944100, 2012CB945004]
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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-gamma 1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca2+-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.
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