Inducible expression of the gp49B inhibitory receptor on NK cells

Murine NK cells express inhibitory receptors belonging to the C-type lectin -like (Ly-49, CD94/NKG2) and Ig superfamily-related (gp49) receptors, The m urine gp49B receptor displays structural homology with human killer inhibit ory receptors, and was previously identified to be a receptor on mast cells and activated NK cells, The gp49B receptor is highly related to gp49A, a r eceptor with unknown function. In this study; using a novel mAb produced ag ainst soluble gp49B molecules that cross-reacts with gp49A, we examined the cellular distribution and function of these receptors, gp49 is constitutiv ely expressed on cells of the myeloid lineage throughout development, as we ll as on mature cells, Importantly, gp49 is not expressed on spleen- and li ver-derived lymphocytes, including NK cells, but its expression is induced in vitro on NK cells following IL-2 stimulation, or in vivo by infection wi th murine CMV, Molecular studies revealed that both the immunoreceptor tyro sine-based inhibitory motif-containing gp49B as well as immunoreceptor tyro sine-based inhibitory motif-less gp49A receptors are up-regulated on NK cel ls following murine CMV infection. When co-cross-linked with NK1.1, gp49B c an inhibit NK1.1-mediated cytokine release by NK cells, Taken together, the se studies demonstrate that the expression of gp49B on NK cells is regulate d, providing the first example of an in vivo activation-induced NK cell inh ibitory receptor, in contrast to the constitutively expressed Ly49 family.