The immunological synapse as a pharmacological target. (August 2018)

• Record Type: Journal Article
• Authors: Finetti, Francesca; Baldari, Cosima T.
• Is Part Of: Pharmacological research. Volume 134(2018)
• Page Start: 118
• Page End: 133
• Publication Date: 2018-08
• Subjects: AP-1 activating protein 1 -- APC antigen presenting cell -- CAR chimeric antigen receptors -- Cbl-b casitas B-lineage lymphoma -- DAG diacylglycerol -- cSMAC central supramolecular activation cluster -- CTLA4 cytotoxic T lymphocyte antigen 4 -- dSMAC distal supramolecular activation cluster -- IFT intraflagellar transport -- IP3 inositol-1, 3, 5-trisphosphate -- IS immunological synapse -- ITAM immunoreceptor tyrosine-based activation motifs -- LAT linker for activation of T cells -- LFA-1 lymphocyte function-associated antigen -- Lck lymphocyte-specific protein tyrosine kinase -- MVBs multivesicular bodies -- NFAT nuclear factor of activated T cells -- NF-κB nuclear factor-κB -- PD1 programmed cell death 1 -- PKC protein kinase C -- PLCγ phospholipase Cγ -- pMHC peptide-major histocompatibility complex ligand -- pSMAC peripheral supramolecular activation cluster -- SNARE soluble N-ethylmaleimide sensitive factor attachment protein receptor -- TCR T cell antigen receptor -- VLA-4 very late activation antigen-4 -- Vps4 vacuolar protein sorting 4 -- ZAP-70 ζ-associated kinase of 70 kDa; Immunological synapse -- Immunotherapy -- T cell receptor -- Co-Stimulatory receptor -- Co-Inhibitory receptor -- Integrin; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2018.06.009
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: The development of T cell mediated immunity relies on the assembly of a highly specialized interface between T cell and antigen presenting cell (APC), known as the immunological synapse (IS). IS assembly is triggered when the T cell receptor (TCR) binds to specific peptide antigen presented in association to the major histocompatibility complex (MHC) by the APC, and is followed by the spatiotemporal dynamic redistribution of TCR, integrins, co-stimulatory receptors and signaling molecules, allowing for the fine-tuning and integration of the signals that lead to T cell activation. The knowledge acquired to date about the mechanisms of IS assembly underscores this structure as a robust pharmacological target. The activity of molecules involved in IS assembly and function can be targeted by specific compounds to modulate the immune response in a number of disorders, including cancers and autoimmune diseases, or in transplanted patients. Here, we will review the state-of-the art of the current therapies which exploit the IS to modulate the immune response.