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RESEARCH PRODUCT

A role for TASK2 channels in the human immunological synapse.

Thomas BuddeJoseph AndronicStefan BittnerTobias RuckManuela CerinaVladimir L. SukhorukovSven G. MeuthKarl-heinz SmallaMarkus SauerStjepana KovacDaniela C. DieterichDmitri SisarioLukas GolaJuncal Fernandez-orthLeoni RolfesThilo KähnePeter Landgraf

subject

0301 basic medicineMaleCD3 ComplexImmunological SynapsesT cellCD3T-LymphocytesImmunologyCellGene ExpressionStimulationImmunological synapseAutoimmune Diseases03 medical and health sciencesJurkat CellsMice0302 clinical medicinePotassium Channels Tandem Pore DomainCell Line TumorGene expressionmedicineExtracellularImmunology and AllergyAnimalsHumansCells CulturedKv1.3 Potassium Channelbiologyβ-tubulin ; TASK2 ; immunological synapse ; dSTORM ; T cellCell MembraneDepolarizationIntermediate-Conductance Calcium-Activated Potassium ChannelsCell biologyMice Inbred C57BL030104 developmental biologymedicine.anatomical_structurebiology.proteinCalciumFemale030215 immunology

description

The immunological synapse is a transient junction that occurs when the plasma membrane of a T cell comes in close contact with an APC after recognizing a peptide from the antigen-MHC. The interaction starts when CRAC channels embedded in the T cell membrane open, flowing calcium ions into the cell. To counterbalance the ion influx and subsequent depolarization, Kv 1.3 and KCa3.1 channels are recruited to the immunological synapse, increasing the extracellular K+ concentration. These processes are crucial as they initiate gene expression that drives T cell activation and proliferation. The T cell-specific function of the K2P channel family member TASK2 channels and their role in autoimmune processes remains unclear. Using mass spectrometry analysis together with epifluorescence and super-resolution single-molecule localization microscopy, we identified TASK2 channels as novel players recruited to the immunological synapse upon stimulation. TASK2 localizes at the immunological synapse, upon stimulation with CD3 antibodies, likely interacting with these molecules. Our findings suggest that, together with Kv 1.3 and KCa3.1 channels, TASK2 channels contribute to the proper functioning of the immunological synapse, and represent an interesting treatment target for T cell-mediated autoimmune disorders.

10.1002/eji.201948269https://pubmed.ncbi.nlm.nih.gov/33169379