Our research studies are directed toward understanding the structure and function of human interferon alphas (IFN-alpha) and their receptors. The objective of these studies is to delineate the rational for the existence of this family of structurally-related proteins and to understand the mechanism by which they elicit their pleiotropic biological activities. To date, 18 major and 4 minor components of human IFN-alpha derived from Sendai virus-induced human lymphoblastoid cells (Namalwa) were isolated by sequential monoclonal antibody affinity chromatography using four different monoclonal antibodies, ultrafiltration and reverse-phase high performance liquid chromatography. Many biological properties of these components have been examined including their antiviral activity on human, bovine and murine cell lines, antiproliferative activity on U937 and Daudi cells, their relative affinities for IFN-alpha 2b binding sites on U937 and Daudi cells, enhancement of the expression of Class I histocompatibility antigens, induction of IL-1, induction of monocyte tumoricidal activity and enhancement of natural killer cell activity.. We are currently examining their antiretroviral properties. Chemical characterization of these IFN-alpha components has also been a major program in our laboratory. Their apparent molecular weights, amino acid compositions and N-terminal amino acid sequences have been determined for all of the isolated components. We are currently studying the carbohydrate structure of the IFN-alpha components as we have identified 3 major glycosylated components and 11 components with low levels of glycosylation. Our group is responsible for the regulatory physicochemical testing of all cytokine products as well as the lot release testing and review of 2 recombinant and 1 natural preparations of IFN-alpha and one recombinant IFN-gamma. Potency assays for these products are performed on a routine basis. Our group participates in the inspection program and in the review of cytokine and growth factor INDs, PLAs and ELAs.
