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). 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 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 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.
Developing T cells form an immunological synapse for passage through the β-selection checkpoint
K. Pham’s present address is Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, and Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
A.H. Allam’s present address is Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia.
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Amr H. Allam, Mirren Charnley, Kim Pham, Sarah M. Russell; Developing T cells form an immunological synapse for passage through the β-selection checkpoint. J Cell Biol 1 March 2021; 220 (3): e201908108. doi: https://doi.org/10.1083/jcb.201908108
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