Second Messenger Systems in a Novel t-Cell Activation Pathway Involving the UM4D4 Surface Antigen
Kim, Timothy S.
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Clinical studies and animal experiments have shown that the pathogenesis of rheumatoid arthritis (RA) is due to autoimmune responses facilitated by T (thymic-derived) lymphocytes. To characterize novel activation pathway of synovial T lymphocytes, a monoclonal antibody against a rheumatoid synovial T cell line has been produced, termed anti- UM4D4. This antibody recognizes a surface antigen, termed UM4D4, expressed strongly on rheumatoid synovial T cells (50- 95%), while present on only 20-25%% of peripheral blood T cells (Higgs et al., 1988). Careful study of Ca++ flux, Inositol phospholipid turnover, and protein kinase C activation following UM4D4 activation would be the next logical step to further study this activation pathway. In this paper, strong evidence of Ca++ Influx following UM4D4 actlvati0n is presented. Working protocols for Inositol trisphosphate (IP3) and protein kinase C (PKC) assays for UM4D4 activation are also discussed. Detalied structural and functional characterization of the UM4D4 antigen in future could facilitate the greater understanding of T-cell activation in rheumatoid arthritis, necessary for possible novel therapeutic approaches.