A NOVEL SURFACE-MOLECULE HOMOLOGOUS TO THE P58 P50 FAMILY OF RECEPTORS IS SELECTIVELY EXPRESSED ON A SUBSET OF HUMAN NATURAL-KILLER-CELLS AND INDUCES BOTH TRIGGERING OF CELL FUNCTIONS AND PROLIFERATION/

Human natural killer (NK) cells express inhibitory (p58) or activatory (p50) receptors for HLA-C alleles. Here, we describe a novel member o f the p58/p50 family that is expressed by a subset of NK cells in abou t one third of donors. This molecule, termed p50.3, mediates NK cell t riggering as revealed by the induction of intracellular free calcium m obilization, cytokine release and cytotoxicity. In addition, anti-p50. 3 monoclonal antibody (mAb) induced a selective, strong proliferation of p50.3(+) NK cells in peripheral blood lymphocytes. Although p50.3 m olecules do not appear to display an obvious HLA class I specificity, they are usually coexpressed with known inhibitory receptors for HLA c lass I alleles. mAb-mediated cross-linking of these receptors leads to inhibition of the anti-p50.3 mAb-induced NK cell activation and proli feration. Surface p50.3 molecules are glycoproteins of similar to 55-5 8 kDa which, upon deglycosylation, display a relative molecular mass o f 36 kDa, similar to that of deglycosylated (activatory) p50 receptors . Analysis of the two-dimensional peptide maps of the 50.3 molecules r evealed a high homology with the other HLA-C-specific p58/p50 receptor s. The use of a set of oligodeoxynucleotide primers, previously shown to amplify the activatory (p50) forms of HLA-C-specific receptors, con sistently amplified in p50.3(+) clones a cDNA sequence termed KKA3. Th is sequence belongs to the p58/p50 multigene family, that encodes for a transmembrane protein specifically stained by anti-p50.3 mAb in cell transfectants. Similar to p50 molecules, the KKA3-encoded molecules a re characterized by two extracellular immunoglobulin-like domains, by the presence of a lysine in the transmembrane region and a short (39 a mino acids) cytoplasmic tail which does not contain immune receptor ty rosine-based activation motifs (ITAM)-like sequences.