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Front. Immunol. | doi: 10.3389/fimmu.2018.00390

NKG2H-expressing T cells negatively regulate T cell responses

  • 1Immunology and Oncology, Consejo Superior de Investigaciones Científicas (CSIC), Spain

The biology and function of NKG2H receptor, unlike the better characterised members of the NKG2 family NKG2A, NKG2C and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signalling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody, we have characterised the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of PBMC, and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-crosslinking of this receptor with an NKG2H-specific monoclonal antibody led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A or NKG2C specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.

Keywords: NKG2H, T cells, Negative regulation, DAP12, cell-cell interaction

Received: 17 Jul 2017; Accepted: 12 Feb 2018.

Edited by:

Rene De Waal Malefyt, Merck (United States), United States

Reviewed by:

Christoph Wülfing, University of Bristol, United Kingdom
David B. Rosen, Merck (United States), United States  

Copyright: © 2018 Dukovska, Fernandez-Soto, Vales-Gomez and Reyburn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Hugh T. Reyburn, Consejo Superior de Investigaciones Científicas (CSIC), Immunology and Oncology, CNB, Darwin 3, Campus de CantoBlanco, Madrid, 28049, Spain, htreyburn@cnb.csic.es