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

Abstract

NK cells acquire the ability to recognize MHC class I molecules during development. Studies with Qa-1b tetramers (Qa-1 tetramers) showed that nearly all NK1.1+ cells from newborn C57BL/6 mice express Qa-1-binding receptors. Cytotoxic activity of these cells is fully inhibited by Qa-1 ligands on target cells. In contrast, neither receptors for H-2Kb nor H-2Db were observed on NK1.1+ cells from newborn mice. After birth, frequencies of Qa-1 tetramer+/NK1.1+ cells gradually decrease as the number of Ly49+/NK1.1+ 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-binding receptors appears largely independent of host MHC class I molecules, as observed in studies using β2-microglobulin-deficient (β2m(-/-)) mice as well as Kb/D(b-/-) and Kb/Db/β2m(-/-) mice. The present results suggest that Qa-1-binding receptors play an important role in the specificity of developing NK cells, and suggest that these cells rely mainly on inhibitory receptors specific for non-classical MHC class I molecules to maintain self tolerance during the first weeks of life.