We will extend recent observations 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 Iymphocytes in response to allogeneic, but not by mitogenic, stimuli and anti-ARAg monoclonal antibody (mAb) PIC5 specifically blocks this alloactivation response in vitro. There are two aims of this proposal: I) 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 repertusion injury.Awardee's statement of the potential commercial applications of the research:Based on our findings that ARAg appears to be important for aTlogeneic activation of T lymphocytess the research proposed herein will determine the feasibility of developing ARAg-based therapeutics which may prove effective in combating the enormous clinical challenges of allograft rejection and GVHD. Such commercial products may include monolclonal antibodies and genetically engineered proteins designed to antagonize inflammatory processes influenced by ARAg.National Institute of Allergy and Infectious Diseases (NIAID)
