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NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor

A G Brooks1, P E Posch, C J Scorzelli

  • 1Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.

The Journal of Experimental Medicine
|February 17, 1997
PubMed

Insights

Natural killer (NK) cells utilize CD94 and NKG2A proteins to regulate immune responses. This study reveals NKG2A is covalently linked to CD94, impacting NK cell function and inhibitory signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD94, a C-type lectin on NK and T cells, is implicated as a receptor for HLA class I molecules.
  • Previous research indicated CD94 associates with an unknown protein.
  • The function of CD94 in NK cell inhibition requires further elucidation.

Purpose of the Study:

  • To identify the 43-kD protein associated with CD94.
  • To characterize the functional consequences of the CD94-NKG2A association on NK cells.

Main Methods:

  • Immunoprecipitation and Western blotting to identify protein associations.
  • Analysis of protein glycosylation patterns.
  • Functional assays using NK cell clones and anti-CD94 monoclonal antibodies.

Main Results:

  • NKG2A, a 43-kD protein, is covalently associated with CD94 on NK cell surfaces.
  • NKG2A surface expression and proper glycosylation depend on its association with CD94.
  • NKG2A expression correlates with CD94-mediated inhibition of NK cell killing.
  • NKG2A possesses immunoreceptor tyrosine-based inhibitory motifs.

Conclusions:

  • NKG2A is the previously unidentified 43-kD protein associated with CD94.
  • The CD94-NKG2A complex functions as an inhibitory receptor on NK cells.
  • NKG2A's inhibitory motifs mediate negative signaling, similar to Ly49 and KIRs.

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