期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201908108
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资金
- Centre for Advanced Histology and Microscopy at the Peter MacCallum Cancer Centre
- L.E.W. Carty Charitable Fund
- Australian Research Council [FT0990405]
- National Health and Medical Research Council [APP1099140]
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) [PA00P3_142120, P300P3_154664]
- Swinburne University Postgraduate Research Award
- Swiss National Science Foundation (SNF) [PA00P3_142120] Funding Source: Swiss National Science Foundation (SNF)
- Australian Research Council [FT0990405] Funding Source: Australian Research Council
Developing T cells establish an immunological synapse at the beta-selection checkpoint, which regulates pre-TCR signaling and promotes passage through this checkpoint. The immunological synapse integrates signals from Notch, CXCR4, and MHC to facilitate transition beyond the beta-selection checkpoint.
The beta-selection checkpoint of T cell development tests whether the cell has recombined its genomic DNA to produce a functional T cell receptor beta (TCR beta). Passage through the beta-selection checkpoint requires the nascent TCR protein to mediate signaling through a pre-TCR complex. In this study, we show that developing T cells at the beta-selection checkpoint establish an immunological synapse in in vitro and in situ, resembling that of the mature T cell. The immunological synapse is dependent on two key signaling pathways known to be critical for the transition beyond the beta-selection checkpoint, Notch and CXCR4 signaling. In vitro and in situ analyses indicate that the immunological synapse promotes passage through the beta-selection checkpoint. Collectively, these data indicate that developing T cells regulate pre-TCR signaling through the formation of an immunological synapse. This signaling platform integrates cues from Notch, CXCR4, and MHC on the thymic stromal cell to allow transition beyond the beta-selection checkpoint.
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