Natural killer (NK) cells and killer (K) cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGLs). Studies continue to define the receptors and structures involved in NK recognition. Previously, a monoclonal antibody (mAb) was developed against NK-target antigens on K562 cells that blocked LGL binding and lysis. We have utilized an anti-idiotypic antibody (anti-ID) to study and characterize the NK receptor and aid in its identification. This anti-ID antibody is reactive with an effector cell protein and blocks LGL binding and target cell lysis. Utilizing this rabbit anti-ID, an expression library from CD3- LGL was screened and specific cDNA clones were isolated. The cDNA coded for a unique 7 kB mRNA that consisted of several distinct structural domains. The NH2- terminal domain was 50% homologous to cyclophilin, a cyclosporin binding protein. Based on the predicted amino acid sequence from this cDNA, anti-peptide antisera were prepared to further examine the structure- function relationship of this novel surface moiety involved in NK lytic function. The molecular and biochemical events involved in lymphocyte-mediated cytolysis are under extensive investigation. In particular, several cytoplasmic granule proteins of CTL and NK cells, including pore-forming protein (PFP, perforin or cytolysin) and serine esterases, have been extensively studied. PFP is the major cytolytic protein of the granules and represents an important structural component of the pore-formation and granule exocytosis models for lymphocyte-mediated cytotoxicity. Recently, we have examined the regulation of PFP mRNA in human peripheral blood T cells and LGL and their role in cell-mediated lysis.
