P58 MOLECULES AS PUTATIVE RECEPTORS FOR MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I MOLECULES IN HUMAN NATURAL-KILLER (NK) CELLS - ANTI-P58 ANTIBODIES RECONSTITUTE LYSIS OF MHC CLASS-I-PROTECTED CELLS IN NKCLONES DISPLAYING DIFFERENT SPECIFICITIES

Human CD3-16+56+ natural killer (NK) cells have been shown to display a clonally distributed ability to recognize major histocompatibility c omplex (MHC) class I alleles. Opposite to T lymphocytes, in NK cells, specific recognition of MHC class I molecules appears to induce inhibi tion of cytolytic activity and, thus, to protect target cells. Since a precise correlation has been established between the expression of th e NK-specific GL183 and EB6 surface molecules (belonging to the novel p58 molecular family) and the specificity of NK clones, we analyzed wh ether p58 molecules could function as receptors for MHC in human NK ce lls. NK clones displaying the previously defined ''specificity 2'' and characterized by the GL183+EB6+ phenotype, specifically recognize the Cw3 allele and thus fail to lyse the FcgammaR+ P815 target cells tran sfected with Cw3. On the other hand, NK clones displaying ''specificit y 1'' and expressing the GL183-EB6+ phenotype failed to lyse Cw4+ targ et cells. Addition of the F(ab')2 fragments of either GL183 or EB6 mAb as well as the XA141 mAb of IgM isotype (specific for the EB6 molecul es) completely restored the lysis of Cw3-transfected P815 cells by the Cw3-specific NK clones EX2 and EX4. Similarly, both the entire EB6 mA b, its F(ab')2 fragment and the XA141 mAb reconstituted the lysis of C 1R, a FcgammaR- target cell expressing Cw4 as the only serologically d etected class I antigen. Thus, it appears that masking of different me mbers of p58 molecules prevents recognition of ''protective'' MHC clas s I alleles and thus the delivering of inhibitory signals. Further sup port to the concept that p58 molecules represent a NK receptor deliver ing a negative signal was provided by experiments in which the entire anti-p58 mAbs (of IgG isotype) could inhibit the lysis of unprotected FcgammaR+ P815 target cells, thus mimicking the inhibitory effect of M HC class I molecules.