STRUCTURE AND FUNCTION OF CD32 ON NK CELLS

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An understanding of the biology and in vivo significance of natural killer cells is a primary focus of many of the investigators in the Immunology Program of the Pittsburgh Cancer Institute (PCI). The rapid translation of laboratory findings into clinical protocols, especially in the area of Biologic Response Modifiers and immunotherapy is of particular interest. This includes approaches such as the use of adoptive cellular immunotherapy, cytokine therapy and the use of other natural biological products such as high dose intravenous immunoglobulin (IVIG) therapy. In regards to the investigation of the potential for IVIG therapy, there has been a long term, research collaboration among investigators at the PCI and at the Bucharest Center for Immunology (BCI) focused on the expression and function of Fc receptors (FcR) on NK cells and effects of IgG binding on NK cell physiology. As a result of these interactions, we have recently demonstrated for the first time the expression of Fc/gamma/RII (CD32) on some human NK cells. These data are of particular interest, as it is commonly accepted that NK cells express only Fc/gamma/RIII (CD16)), the low affinity receptor for IgG. As expression of these Fc/gamma/R, and their interactions with IgG is of significance for the evaluation of IVIG therapy, it is of importance that the nature NK cell-associated isoform(s) of CD32 to be elucidated. Based upon our findings, we propose to characterize the biochemical, molecular and functional features of NK cell-associated CD32, and compare those features with the known forms of CD32 and with CD16. Our specific aims include: 1. Biochemical characterization of NK cell-associated Fc/gamma/RII (CD32) and the determination of the expression of a single or multiple isoforms of this receptor by NK cells. 2. Molecular characterization of specific cDNA(s) encoding the NK cell- associated isoform(s) of Fc/gammam/RII (CD32). 3. Determination of the ligand binding characteristics of the NK cell associated Fc/gamma/RII isoform(s). 4. Functional analyses of NK cell-associated Fc/gamma/RII. The results of these studies will be of significance both from the standpoint of increased understanding of the nature and distribution of CD32, the activation of certain functions such as cytotoxicity and cytokine production by NK cells, and the potential effects of IVIG therapy on NK cell function.