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DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo

Ilaria Tassi1, Gaelle Le Friec, Susan Gilfillan

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. itassi@pathology.wustl.edu

European Journal of Immunology
|February 28, 2009
PubMed

Insights

Natural killer (NK) cells use adaptors like DAP10 and DAP12 for signaling. While Ly49H and Ly49D receptors associate with DAP10, this interaction has minimal impact on NK cell function and viral control.

Area of Science:

  • Immunology
  • Cellular Signaling
  • Innate Immunity

Background:

  • Activating receptors on natural killer (NK) cells utilize transmembrane adaptors, including DAP10, DAP12, and FcR-gamma, to transmit intracellular signals.
  • These adaptors initiate distinct signaling pathways, influencing the NK cell response, with DAP10 primarily mediating cytotoxicity and DAP12 inducing both cytotoxicity and IFN-gamma secretion.
  • While NKG2D signaling involves both DAP10 and DAP12, initial studies suggested Ly49H and Ly49D receptors exclusively recruit DAP12, with recent findings proposing a DAP10 association.

Purpose of the Study:

  • To investigate whether DAP10 associates with Ly49H and Ly49D receptors in primary NK cells.
  • To determine the functional significance of the DAP10 association with Ly49H and Ly49D under physiological conditions.

Main Methods:

  • Analysis of DAP10 association with Ly49H and Ly49D in primary NK cells.
  • Assessment of the impact of DAP10 association on receptor cell surface expression.
  • Evaluation of Ly49H-mediated control of murine cytomegalovirus (MCMV) infection in the context of DAP10 association.

Main Results:

  • Data confirm that DAP10 associates with both Ly49H and Ly49D receptors in primary NK cells.
  • This association contributes marginally to the cell surface expression levels of Ly49H and Ly49D.
  • The association of DAP10 with Ly49H did not result in a significant impact on Ly49H-mediated control of murine cytomegalovirus infection.

Conclusions:

  • Activating NK-cell receptors can exhibit promiscuity in adaptor association, interacting with multiple adaptors like DAP10 and DAP12.
  • The functional consequences of such adaptor promiscuity can vary significantly and may not always be apparent in all contexts.
  • Despite association, DAP10 engagement with Ly49H and Ly49D does not appear critical for Ly49H-mediated antiviral immunity in this model.

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