Novel Leukocyte Receptor and Allograft Rejection

We will extend recent observations regarding the discovery and characterization of alloreaction-a-ssociated antigen (ARAg), a novel member of the immunoglobulin gene superfamily selectively expressedon 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 thisalloactivation response in vitro. There are two aims of this proposal: 1) to provide evidence for theexistence of a putative ARAg counter-receptor (ARAg-CR) expressed which presumably interacts withARAg in transduction of important activation signals, and 2) to isolate a cDNA clone encoding the murinehomologue of ARAg. Soluble recombinant ARAg proteins will be engineered and used in flow cytometryassays to examine phenotypic expression of the putative ARAg-CR on relevant cell types. Evidence forthe existence of a putative ARAg-CR will provide an additional target for potential pharmacologicintervention. Molecular cloning of the murine ARAg homologue is essential for development of an animalmodel in which to evaluate candidate ARAg-based therapeutics in vivo. The long-term objective of thisproject is to develop ARAg-related reagents for their potential therapeutic value in allograft rejection andGVHD as well as autoimmune disease and reperfusion injury.