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

Allam, AH; Charnley, M; Pham, K; Russell, SM

Author(s): Allam, AH; Charnley, M; Pham, K; Russell, SM;
Details: Publication Year 2021-03,Volume 220,Issue #3,Page e201908108
Journal Title: Journal of Cell Biology
Publication Type: Research article
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 (TCRbeta). Passage through the beta-selection checkpoint requires the nascent TCRbeta 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 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 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.
Keywords: Actins/metabolism; Adaptor Proteins, Signal Transducing/metabolism; Animals; Cell Polarity; Cell Proliferation; Humans; Immunological Synapses/*metabolism; Major Histocompatibility Complex; Membrane Proteins/metabolism; Mice, Inbred C57BL; Microtubule-Organizing Center/metabolism; Models, Biological; Molecular Mimicry; Receptors, Antigen, T-Cell, alpha-beta/*metabolism; Receptors, CXCR4/metabolism; Receptors, Notch/metabolism; Signal Transduction; Stromal Cells/metabolism; T-Lymphocytes/cytology/*immunology; Thymus Gland/metabolism
Department(s): Laboratory Research
PubMed ID: 33464309
Publisher's Version: https://doi.org/10.1083/jcb.201908108
Open Access at Publisher's Site: https://doi.org/10.1083/jcb.201908108
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-23 04:02:53

Last Modified: 2025-05-23 04:04:10