ALTERED PHENOTYPE AND FUNCTION OF NATURAL-KILLER-CELLS EXPRESSING THE MAJOR HISTOCOMPATIBILITY COMPLEX RECEPTOR LY-49 IN MICE TRANSGENIC FOR ITS LIGAND

The Ly-49 molecule has been shown to interact with major histocompatibility complex (MHC) class I molecules, and the lytic function of Ly-49(+) natural killer (NK) cells from C57BL/(6) (H-2(b)) mice is inhibited by the recognition of H-2D(d) on tumor target cells, Introduction of a Ly-49 ligand, H-2D(d), into C57BL/6 mice did not alter the percentage of Ly-49(+) NK cells (13-18%), but it led to three functional effects on this subset. (i) The Ly-49 expression in the positive population was reduced by 30-50% compared to C57BL/6 control mice, (ii) While this Ly-49(+) subset (Ly-49lo) in the transgenic mice failed to kill BALB/c concanavalin A (Con A) blasts, which have high H-2D(d) expression, it was capable of killing SP2/O tumor cells, which have low H-2D(d) expression. Ly-49(+) NK cells (Ly-49hi) from nontransgenic mice failed to kill both of these H-2D(d)-expressing target cells, (iii) In the transgenic mice, the Ly-49(+) subset acquired the ability to kill C57BL/6 Con A blasts, in contrast to the Ly-49(+) NK cells of C57BL/6 mice, We propose a ''receptor-calibration'' hypothesis, where low receptor density on the effector cells imposed by selection or adaptation to the environment allows higher sensitivity for detection of reduced self-MHC ligands on potential target cells.