Coordinated expression of DNAM-1 and LFA-1 in educated NK cells

J Immunol. 2015 May 1;194(9):4518-27. doi: 10.4049/jimmunol.1401972. Epub 2015 Mar 30.

Abstract

The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I-specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / genetics*
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Biomarkers
  • Gene Expression*
  • Humans
  • Immunological Synapses / genetics
  • Immunological Synapses / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / genetics*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / metabolism

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Biomarkers
  • CD226 antigen
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Natural Killer Cell