The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/2/795/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 4, February 17, 1997 795-800

Brief Definitive Reports

NKG2A Complexed with CD94 Defines a Novel Inhibitory Natural Killer Cell Receptor

Andrew G. Brooks, Phillip E. Posch, Christopher J. Scorzelli, Francisco Borrego, and John E. Coligan

From Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852

CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

Address correspondence to John E. Coligan, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852.

Note added in proof: Since the original submission of this manuscript similar results including a description of the NKG2A/B-specific mAb 1A12 were reported by Lazetic et al. (Lazetic, S., C. Chang, J.P. Houchins, L.L. Lanier, and J.H. Phillips. 1996. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J. Immunol. 157:4741–4745).


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