Expression of Ly49A on T cells alters the threshold for T cell responses

In this study we investigated the balance between activating and inhibitory signals during T cell activation. We have used transgenic mice in which CD 8(+) T cells expressed an inhibitory receptor, Ly49A, and a specific activa ting alpha beta TCR. This TCR recognizes an lymphocytic choriomeningitis vi rus peptide in combination with H-2D(b). We observed a quantitative influen ce on cellular responses that depended upon the activating signals received through the TCR and the inhibitory signals received through Ly49A. By vary ing the peptide concentration given to stimulating cells or target cells, w e could adjust the amount of ligand available to trigger the TCR. At low do ses of peptide, Ly49A-expressing T cells were unresponsive on target cells that expressed H-2D(d), but responded against target cells without H-2Dd. H owever, this inhibition could be overcome by increasing the peptide concent ration or by addition of anti-Ly49A F(ab')(2) fragments. Thus, rather than behaving as simple "off" switches, our data indicate that Ly49 receptors mo dulate T cell signaling so that higher amounts of activating signals are re quired for effector-cell responses.