A role for TASK2 channels in the human immunological synapse

Eur J Immunol. 2021 Feb;51(2):342-353. doi: 10.1002/eji.201948269. Epub 2020 Dec 18.

Abstract

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.

Keywords: T cell; TASK2; dSTORM; immunological synapse; β-tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • CD3 Complex / immunology
  • Calcium / immunology
  • Cell Line, Tumor
  • Cell Membrane / immunology
  • Cells, Cultured
  • Female
  • Gene Expression / immunology
  • Humans
  • Immunological Synapses / immunology*
  • Intermediate-Conductance Calcium-Activated Potassium Channels / immunology
  • Jurkat Cells
  • Kv1.3 Potassium Channel / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Potassium Channels, Tandem Pore Domain / immunology*
  • T-Lymphocytes / immunology

Substances

  • CD3 Complex
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnk5 protein, mouse
  • Kv1.3 Potassium Channel
  • Potassium Channels, Tandem Pore Domain
  • Calcium