Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b).
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-1(b), we provide direct evidence that CD94/NKG2A recognizes Qa-1(b). We further demonstrate that NK recognition of Qa-1(b) results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1(b)-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.
Vance
R E
RE
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California Berkeley, Berkeley, California 94720, USA.
Kraft
J R
JR
Altman
J D
JD
Jensen
P E
PE
Raulet
D H
DH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D019556:COS Cells; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000276:immunology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection / Q000235:genetics
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D011956:Receptors, Cell Surface