Cellular and molecular signaling towards T cell immunological self-tolerance.

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Signal Transduction*/immunology ; Self Tolerance*/immunology ; Receptors, Antigen, T-Cell*/immunology ; Receptors, Antigen, T-Cell*/metabolism; Humans ; Animals ; T-Lymphocytes, Regulatory/immunology ; Lymphocyte Activation
    • Abstract:
      The binding of a cognate antigen to T cell receptor (TCR) complex triggers a series of intracellular events controlling T cell activation, proliferation, and differentiation. Upon TCR engagement, different negative regulatory feedback mechanisms are rapidly activated to counterbalance T cell activation, thus preventing excessive signal propagation and promoting the induction of immunological self-tolerance. Both positive and negative regulatory processes are tightly controlled to ensure the effective elimination of foreign antigens while limiting surrounding tissue damage and autoimmunity. In this context, signals deriving from co-stimulatory molecules (i.e., CD80, CD86), co-inhibitory receptors (PD-1, CTLA-4), the tyrosine phosphatase CD45 and cytokines such as IL-2 synergize with TCR-derived signals to guide T cell fate and differentiation. The balance of these mechanisms is also crucial for the generation of CD4 + Foxp3 + regulatory T cells, a cellular subset involved in the control of immunological self-tolerance. This review provides an overview of the most relevant pathways induced by TCR activation combined with those derived from co-stimulatory and co-inhibitory molecules implicated in the cell-intrinsic modulation of T cell activation. In addition to the latter, we dissected mechanisms responsible for T cell-mediated suppression of immune cell activation through regulatory T cell generation, homeostasis, and effector functions. We also discuss how imbalanced signaling derived from TCR and accessory molecules can contribute to autoimmune disease pathogenesis.
      Competing Interests: Conflict of interest The authors declare that they have no conflicts of interests with the contents of this article.
      (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: CD45; CTLA-4; IL-2; TCR; immunological self-tolerance; regulatory T cells
    • Accession Number:
      0 (Receptors, Antigen, T-Cell)
    • Publication Date:
      Date Created: 20240303 Date Completed: 20240427 Latest Revision: 20240521
    • Publication Date:
      20240521
    • Accession Number:
      PMC10981134
    • Accession Number:
      10.1016/j.jbc.2024.107134
    • Accession Number:
      38432631