β3 subunit of Na,K ATPase regulates T cell activation with no involvement of Na,K ATPase activity

Immunobiology. 2015 May;220(5):634-40. doi: 10.1016/j.imbio.2014.11.017. Epub 2015 Jan 29.

Abstract

Na,K ATPase plays an important role in the regulation of Na(+) and K(+) ions that are required for normal resting membrane potential and various cellular functions. Na,K ATPase is composed of two subunits, α and β subunits. Engagement of the β subunit by an agonistic monoclonal antibody (mAb) P-3E10 inhibited T cell activation and induced the G0/G1 cell cycle arrest. In addition, mAb P-3E10 decreased CD25 expression. The mAb P-3E10, however, did not inhibit the proliferation of cell lines and the phagocytosis activity of phagocytes, and did not interfere with the Na,K ATPase activity. These results indicate that mAb P-3E10 reacts to the β subunit and, as a consequence, brings about the regulation of the T cell activation without disturbing the Na,K pump activity. By sequential immunoprecipitation, we demonstrated the expression of the β3 subunit free form apart from the α subunit. In this study, we propose that the β3 subunits of Na,K ATPase are expressed separately from the α subunit, and play a role in regulation of the immune response.

Keywords: CD298; Monoclonal antibody; Na,K ATPase; T cell activation; β3 subunit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Cell Cycle
  • Cell Membrane / metabolism*
  • Cell Proliferation
  • Humans
  • Ion Transport
  • Jurkat Cells
  • Lymphocyte Activation
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / immunology
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • T-Lymphocytes / immunology*

Substances

  • ATP1B3 protein, human
  • Antibodies, Monoclonal
  • Sodium-Potassium-Exchanging ATPase