DESCRIPTION (from the application): A rapidly expanding body of evidence now suggests that a newly discovered human gammaherpes virus is a co-factor in the pathogenesis of both Kaposi's sarcoma (KS) and a subset of body cavity based B-cell lymphomas in AIDS patients. Experience with other herpesviruses would indicate that a description of the interaction between this novel virus, currently termed KS-associated herpesvirus (KSHV), and the host immune system will play an important role in understanding the molecular virology of the pathogen, in unravelling the mechanisms of its pathogenesis and for the design of candidate vaccines. It is therefore highly desirable to investigate the human antibody response to KSHV at the molecular level. We propose to use combinatorial antibody library technology to rescue large panels of KSHVspecific monoclonal antibody Fabs from individuals who have generated a humoral response against the virus in the course of natural infection. By screening combinatorial libraries against KSHV infected cells and individual viral antigens, we will build a detailed view of the human antibody response to the virus. The recombinant antibodies will be characterized in terms of antigen and epitope recognized, amino acid sequence and neutralizing ability in vitro. These novel reagents will serve as probes to further investigate the hypothesized role of KSHV in tumorigenesis.