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Inducible expression of the gp49B inhibitory receptor on NK cells

L L Wang1, D T Chu, A O Dokun

  • 1Howard Hughes Medical Institute, Division of Rheumatology, Department of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 9, 2000
PubMed

Insights

Murine NK cells express gp49B, an activation-induced inhibitory receptor. This contrasts with constitutively expressed receptors, offering new insights into NK cell regulation during viral infections.

Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • Murine NK cells utilize inhibitory receptors like Ly-49 and CD94/NKG2.
  • gp49B, structurally similar to human killer inhibitory receptors, is found on mast cells and activated NK cells.
  • gp49A is a related receptor with an unknown function.

Purpose of the Study:

  • To investigate the cellular distribution and function of gp49B and gp49A receptors.
  • To characterize gp49 expression patterns in myeloid and lymphoid cells.
  • To determine the regulation of gp49 expression on NK cells.

Main Methods:

  • Production of a novel monoclonal antibody (mAb) against soluble gp49B, cross-reactive with gp49A.
  • Analysis of gp49 expression on various cell types and under different conditions (in vitro IL-2 stimulation, in vivo murine CMV infection).
  • Molecular studies to assess receptor upregulation and functional assays involving co-cross-linking with NK1.1.

Main Results:

  • gp49 is constitutively expressed on myeloid cells but not on lymphocytes (spleen, liver).
  • gp49 expression is induced on NK cells in vitro (IL-2) and in vivo (murine CMV infection).
  • Both gp49B and gp49A are upregulated on NK cells post-murine CMV infection; gp49B inhibits NK1.1-mediated cytokine release.

Conclusions:

  • gp49B expression on NK cells is regulated, unlike constitutively expressed Ly49 receptors.
  • This study identifies gp49B as the first in vivo activation-induced NK cell inhibitory receptor.
  • Findings provide new understanding of NK cell receptor regulation and function during infection.

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