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

© 2025 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙