Cutting edge: Expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1(+)Ly-49(-) cells: A possible mechanism of tolerance during NK cell development

Fetal liver- and thymus-derived NK1.1(+) cells do not express known Ly-49 r eceptors.-Despite the absence of Ly-49 inhibitory receptors, fetal and neon atal NK1.1(+)Ly-49(-) cells can distinguish between class I-high and I-low target cells, suggesting the existence of other: class L-specific inhibitor y receptors. We demonstrate that fetal NK1.1(+)Ly-49(-) cell lysates contai n CD94 protein and that a significant proportion of fetal NK cells are boun d by Qa1(b) tetramers. Fetal and adult NK cells efficiently lyse lymphoblas ts from K(b-/-)Db(-/-) mice. Qa1(b)- specific peptides Qdm and HLA-CW4 lead er peptide specifically inhibited the lysis of these blasts by adult and fe tal NK cells. Qdm peptide also inhibited the lysis of Qa1(b)-transfected hu man 721.221 cells by fetal NK cells. Taken together, these results suggest that the CD94/NKG2A receptor complex is the major known inhibitory receptor for class I (Qa1(b)) molecules on developing fetal NK cells.