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- W2968829505 abstract "Abstract The β-selection checkpoint of T cell development tests whether the cell has recombined its genomic DNA to produce a functional T Cell Receptor β (TCRβ) receptor. Passage through the β-selection checkpoint requires the nascent TCRβ protein to mediate signaling through a pre-TCR complex. In this study, we show that developing T cells at the β-selection checkpoint establish an immunological synapse in in vitro & 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 β-selection checkpoint, Notch and CXCR4 signaling. In vitro and in situ analyses indicate that the immunological synapse promotes passage through the β-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 β-selection checkpoint. Summary T cell development requires testing whether genomic rearrangement has produced a T cell receptor capable of transmitting signals. Most T cells fail this test. Here, we show that passage through the β-selection checkpoint requires assembly of a platform to support TCR signaling." @default.
- W2968829505 created "2019-08-22" @default.
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- W2968829505 date "2019-08-12" @default.
- W2968829505 modified "2023-10-16" @default.
- W2968829505 title "Developing T cells form an immunological synapse for passage through the β−selection checkpoint" @default.
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- W2968829505 doi "https://doi.org/10.1101/732511" @default.
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