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00925njm 22002777a 4500 dc Rocha-Perugini, Vera author Sanchez-Madrid, Francisco author Martinez del Hoyo, Gloria author 2016 Tetraspanin-enriched microdomains (TEMs) are specialized membrane platforms driven by protein protein interactions that integrate membrane receptors and adhesion molecules. Tetraspanins participate in antigen recognition and presentation by antigen-presenting cells (APCs) through the organization of pattern-recognition receptors (PRRs) and their downstream induced signaling, as well as the regulation of MHC-II-peptide trafficking. T lymphocyte activation is triggered upon specific recognition of antigens present on the APC surface during immunological synapse (IS) formation. This dynamic process is characterized by a defined spatial organization involving the compartmentalization of receptors and adhesion molecules in specialized membrane domains that are connected to the underlying cytoskeleton and signaling molecules. Tetraspanins contribute to the spatial organization and maturation of the IS by controlling receptor clustering and local accumulation of adhesion receptors and integrins, their downstream signaling, and linkage to the actin cytoskeleton. This review offers a perspective on the important role of TEMs in the regulation of antigen recognition and presentation and in the dynamics of IS architectural organization. Front Immunol. 2016; 6:653 10.3389/fimmu.2015.00653 1664-3224 Frontiers in Immunology 26793193 http://hdl.handle.net/20.500.12105/5245 Tetraspanins Tetraspanin-enriched microdomains Adhesion receptors Immunological synapse T-cell activation T-CELL-ACTIVATION MHC CLASS-II HEPATITIS-C VIRUS ADHESION-DEPENDENT ACTIVATION IMMATURE DENDRITIC CELLS TRANSMEMBRANE-4 SUPERFAMILY ENRICHED MICRODOMAINS INTEGRIN ACTIVATION IMMUNE SYNAPSE LIPID RAFTS Function and Dynamics of Tetraspanins during Antigen Recognition and Immunological Synapse Formation