PT  - JOURNAL ARTICLE
AU  - Amr H. Allam
AU  - Mirren Charnley
AU  - Kim Pham
AU  - Sarah M. Russell
TI  - Developing T cells form an immunological synapse for passage through the β−selection checkpoint
AID  - 10.1101/732511
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 732511
4099  - http://biorxiv.org/content/early/2019/08/12/732511.short
4100  - http://biorxiv.org/content/early/2019/08/12/732511.full
AB  - 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.