Identification of NKp80, a novel triggering molecule expressed by human NKcells

The ability of NK cells to kill a wide range of tumor or virally infected t arget cells as well as normal allogeneic T cell blasts appears to depend up on the concerted action of multiple triggering NK receptors. In this study, using two specific monoclonal antibodies [(mAb) MA152 and LAP171], we iden tified a triggering NK receptor expressed at the cell surface as a dimer of approximately 80 kDa (NKp80). NKp80 is expressed by virtually all fresh or activated NK cells and by a minor subset of T cells characterized by the C D56 surface antigen. NKp80 surface expression was also detected in all CD3( -) and in 6/10 CD3(+) large granular lymphocyte expansions derived from pat ients with lymphoproliferative disease of granular lymphocytes. In polyclon al NK cells, mAb-mediated cross-linking of NKp80 resulted in induction of c ytolytic activity and Ca2+ mobilization. A marked heterogeneity existed in the magnitude of the cytolytic responses of different NK cell clones to ant i-NKp80 mAb. This heterogeneity correlated with the surface density of NKp4 6 molecules expressed by different NK clones. The mAb-mediated masking of N Kp80 led to a partial inhibition of the NK-mediated lysis of appropriate al logeneic phytohemagglutinin-induced T cell blasts, while it had no effect o n the lysis of different tumor target cells, including T cell leukemia cell s. These data suggest that NKp80 recognizes a ligand on normal T cells that may be down-regulated during tumor transformation. Molecular cloning of th e cDNA coding for NKp80 revealed a type II transmembrane molecule of 231 am ino acids identical to the putative protein encoded by a recently identifie d cDNA termed KLRF1.