DEVELOPMENTALLY-REGULATED EXTINCTION OF LY-49 RECEPTOR EXPRESSION PERMITS MATURATION AND SELECTION OF NK1.1(-CELLS() T)

Clonally distributed inhibitory receptors negatively regulate natural killer (NK) cell function via specific interactions with allelic forms of major histocompatibility complex (MHC) class I molecules. In the m ouse, the Ly-49 family of inhibitory receptors is found not only on NK cells but also on a minor (NK1.1+) T cell subset. Using Ly-49 transge nic mice, we show here that the development of NK1.1+ T cells, in cont rast to NK or conventional T cells, is impaired when their Ly-49 recep tors engage self-MHC class I molecules. Impaired NK1.1+ T cell develop ment in transgenic mice is associated with a failure to select the app ropriate CD-1-reactive T cell receptor repertoire. In normal mice, NK1 .1+ t cell maturation is accompanied by extinction of Ly-49 receptor e xpression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for norma l NK1.1+ T cell maturation and selection.