Role of Qa-1(b)-binding receptors in the specificity of developing NK cells

NK cells acquire the ability to recognize MHC class I molecules during deve lopment. Studies with Qa-1(b) tetramers (Qa-1 tetramers) showed that nearly all NK1.1(+) cells from newborn C57BL/6 mice express Qa-1 binding receptor s. Cytotoxic activity of these cells is fully inhibited by Qa-1 ligands on target cells. In contrast, neither receptors for H-2K(b) nor H-2D(b) were o bserved on NK1.1(+) cells from newborn mice. After birth, frequencies of Qa -1 tetramer(+)/ NK1.1(+)cells gradually decrease as the number of Ly49(+)/N K1.1(+)cells increases. Cell transfer studies showed that Qa-1 tetramer(+) cells from newborn mice do not lose expression of Qa-1 receptors, but that they further acquire expression of Ly49 molecules. Acquisition of Qa-1-bind ing receptors appears largely independent of host MHC class I molecules, as observed in studies using beta 2-microglobulin-deficient (beta 2m(-/-)) mi ce as well as K-b/Db-/- and K-b/D-b/beta 2m(-/-) mice. The present results suggest that Qa-l-binding receptors play an important role in the specifici ty of developing NK cells, and suggest that these cells rely mainly on inhi bitory receptors specific for non-classical MHC class I molecules to mainta in self tolerance during the first weeks of life.