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J. Exp. Med.,
Volume 188, Number 10, November 16, 1998 1841-1848
By
From the * Department of Molecular and Cell Biology and Cancer Research Laboratory, University of
California Berkeley, Berkeley, California 94720; and the Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors
for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the
cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor,
a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1b, we provide direct evidence that CD94/NKG2A recognizes Qa-1b. We further demonstrate
that NK recognition of Qa-1b results in the inhibition of target cell lysis. Inhibition appears to
depend on the presence of Qdm, a Qa-1b-binding peptide derived from the signal sequences of
some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK
complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings
suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells.
Department of Pathology and Laboratory
Medicine and § Emory Vaccine Center and Department of Microbiology and Immunology, Emory
University School of Medicine, Atlanta, Georgia 30322
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