The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/6/2109/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 12, June 15, 1998 2109-2114

Brief Definitive Reports

Developmentally Regulated Extinction of Ly-49 Receptor Expression Permits Maturation and Selection of NK1.1+ T Cells

H. Robson MacDonald, Rosemary K. Lees, and Werner Held

From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland

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 mouse, 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 transgenic mice, we show here that the development of NK1.1+ T cells, in contrast to NK or conventional T cells, is impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired NK1.1+ T cell development in transgenic mice is associated with a failure to select the appropriate CD1-reactive T cell receptor repertoire. In normal mice, NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor expression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T cell maturation and selection.

Key Words: NK1.1+ T cells • Ly-49 • development • repertoire selection • Ly-49A transgenic mice

Address correspondence to H.R. MacDonald, Ludwig Institute for Cancer Research, Ch. des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41-21-692-59-89; Fax: 41-21-653-44-74; E-mail: hughrobson. macdonald{at}isrec.unil.ch

Werner Held was supported by a grant (31-49137.96) and a START (Swiss Talents for Academic Research and Teaching) fellowship from the Swiss National Science Foundation.


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