MHC class I-Ly49 interactions shape the Ly49 repertoire on murine NK cells

This study aims to determine how the interaction of Ly49 receptors with MHC class I molecules shapes the development of the Ly49 repertoire. We have e xamined the percentage of NK cells that expressed Ly49A, Ly49G2, and Ly49D in single and double Ly49A/C-transgenic mice on four different MHC backgrou nds, H-2(b), H-2(d), H-2(b/d), and beta (2)-microglobulin(-/-). The results show that the total numbers of NK cells were not different among the strai ns. The prior expression of a Ly49 receptor capable of binding to self MHC class I altered the percentage of NK cells expressing endogenous Ly49A, Ly4 9G2, and Ly49D even in mice in which no MHC ligand was present for the latt er receptors. The NK cells in the Ly49-transgenic mice expressed the same l evel of endogenous Ly49 receptors as wild-type mice of a similar MHC backgr ound. In contrast, the number of NK T cells was reduced in mice in which th e Ly49 transgene could bind to a MHC class I molecule. The onset of Ly49 re ceptor expression on NK cells during ontogeny was not altered in the presen ce of transgenic Ly49 receptors. These data support a sequential model and argue against a selection model for Ly49 repertoire development on NK cells .