TRANSGENIC EXPRESSION OF THE LY49A NATURAL-KILLER-CELL RECEPTOR CONFERS CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)-SPECIFIC INHIBITION AND PREVENTS BONE-MARROW ALLOGRAFT-REJECTION

Natural killer (NK) cells and some T cells are endowed with receptors specific for class I major histocompatibility complex (MHC) molecules that can inhibit cellular effector functions. The function of the Ly49 receptor family has been studied in vitro, but no gene transfer exper iments have directly established the role of these receptors in NK cel l functions. We show here that transgenic expression of the H-2D(d)-sp ecific Ly49A receptor in all NK cells and T cells conferred class I-sp ecific inhibition of NK cell-mediated target cell lysis as well as of T cell proliferation. Furthermore, transgene expression prevented NK c ell-mediated rejection of allogeneic H-2(d) bone marrow grafts by irra diated mice. These results demonstrate the function and specificity of Ly49 receptors in vivo, and establish that their subset-specific expr ession is necessary for the discrimination of MHC-different cells by N K cells in unmanipulated mice.