The goal of this proposal is to extend recent observations by the P.I. and colleagues regarding the discovery and characterization of alloreaction- associated antigen (ARAg), a novel member of the immunoglobulin gene superfamily selectively expressed on leukocyte subsets. ARAg surface expression is increased on T lymphocytes in response to allogeneic, but not by mitogenic, stimuli and anti-ARAg monoclonal antibody (mAb) P1C5 specifically blocks this alloactivation response in vitro. The two aims of this SBIR Phase I proposal are: 1) to provide evidence for the existence of a putative ARAg counter-receptor (ARAg-CR) expressed which presumably interacts with ARAg in transduction of important activation signals and 2) to isolate a cDNA clone encoding the murine homologue of ARAg. Soluble recombinant ARAg proteins will be engineered and used in flow cytometry assays to examine phenotypic expression of the putative ARAg-CR on relevant cell types. Evidence for the existence of a putative ARAg-CR will provide an additional target for potential pharmacologic intervention. Molecular cloning of the murine ARAg homologue is essential for development of an animal model in which to evaluate candidate ARAg- based therapeutics in vivo. The long-term objective of this project is to develop ARAg-related reagents for their potential therapeutic value in allograft rejection and GVHD as well as autoimmune disease and reperfusion injury.
