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. 2021 Jan 19;220(3):e201908108. doi: 10.1083/jcb.201908108

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© 2021 Allam et al.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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Figure 10. — A new model for the β-selection checkpoint that incorporates an immunological synapse. In the proposed model, contact of DN3a developing T cells with stromal cells in the thymus (OP9-DL1 in in vitro) causes Notch1 and CXCR4 to engage with their ligands (DL1/4 and CXCRL12, respectively). Notch1 and CXCR4 engagement promotes the establishment of the immunological synapse via the pre-TCR (pTα and TCRβ chains). The immunological synapse is correlated with the polarization of MTOC, clustering of the CD3 complex clustering (ε, δ, and γ chains), and proximity to the MHC on the stromal cell. The immunological synapse then provides the signaling platform required for downstream signal transduction through the pre-TCR. Signaling via the pre-TCR promotes transition beyond the β-selection checkpoint, followed by proliferation and differentiation to the subsequent T cell developmental stages. IS, immunological synapse.