It is becoming evident that gamma/delta (gd) T cells play an important role in defense against bacterial and viral infections as well as in autoimmunity. gd T cells are expanded in humans with infectious diseases such as tuberculosis, salmonellosis, brucellosis, ehlichiosis, tularemia, malaria, leishmaniasis, mononucleosis, and in HIV (early stages). They are expanded in the synovium of patients with sarcoidosis. In contrast to alpha/beta (ab) T cells, which recognize peptide antigens in the context of MHC molecules, the predominant subset of gd T cells in human peripheral blood, termed Vg2Vd2 T cells, having no homologue in rodents, recognize unprocessed nonpeptide phosphate antigens in the absence of professional APC or known antigen presenting molecules. Abundant data describing in detail the interactions of the ab TCR with MHC-bound peptide have deepened our understanding of their role in infectious disease and in autoimmunity. In contrast, there is little information regarding the nature of interaction between the gd TCRs and their ligands. In fact, the identities of most microbial and autoimmune antigens reactive with gd T cells is unknown. Preliminary evidence in the investigator's laboratory shows that the TCR g junctional region is of crucial importance for the recognition of phosphate antigens by Vg2Vd2 T cells, arguing against a superantigen-like recognition of such antigens. The laboratory recently has found that alkylamines, which are major products of certain bacteria that cause gingivitis and many other diseases and are also found in plant foods and human body fluids, cause proliferation of Vg2Vd2 T cells in a TCR-specific manner. Alkylamine antigens are the first phosphate-free antigens described for Vg2Vd2 T cells and thus represent a distinct chemical class of ligand for Vg2Vd2 T cells. The investigator proposes to 1) Define the structural characteristics necessary for bioactivity of alkylamine antigens by testing a panel of naturally occurring alkylamine antigens for reactivity to gd T cells; 2) Identify specific domains and residues in the gd TCR important for recognition of alkylamine and phosphate antigens; 3) Determine the requirements of alkylamine antigens for antigen presentation and processing; 4) Define the phenotypes and alkylamine antigen reactivities of gingival gd T cells from patients with chronic gingivitis.
