It is proposed that a novel synthetic peptide approach be used to determine the nature of the cellular receptor binding site(s) on gamma interferon (IFNY). Both human and mouse IFNY will be studied in competitive binding experiments with synthetic peptides corresponding to IFNY sequences that are likely to appear on the exterior of the molecule. Identification of exterior segments will be on the basis of hydropathic (hydrophilic/hydrophobic) profiles. Fab fragments of antibodies to the synthetic peptides will be reacted with native IFNY in an attempt to corroborate the synthetic peptide binding studies, and to possibly identify sequences of the IFNY molecule that while not responsible for binding, are closely associated sterically with the binding site. By studying both human and mouse IFNY, it is hoped that the structural basis of the species specificity of IFNY will be ascertained, as well as the applicability of the synthetic peptide approach for analysis fo IFNY and other lymphokine/hormone binding sites. The work is of importance because knowledge of the structure of the IFNY binding site may allow one to construct agoniats and antagonists of IFNY, thereby providing the potential to regulate immune responses that can be influenced positively or negatively by IFNY. In addition, much of the information generated should be relevant to understanding better how IFNY mediates its antiviral and cell regulatory effects. (HF)