Developing T cells form an immunological synapse for passage through the β-selection checkpoint

Abstract

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}) receptor. Passage through the {beta}-selection checkpoint requires the nascent TCR{beta} 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 & 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.\n\nSummaryT 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 {beta}-selection checkpoint requires assembly of a platform to support TCR signaling.