A NEW TRIPEPTIDE, POL-509, INFLUENCES BIOCHEMICAL EVENTS ASSOCIATED WITH ANTIGEN PRESENTATION EFFICIENCY OF PPD-SPECIFIC EBV-B CELLS

A synthetic tripeptide (pGLU-LEU-TRP-OCH3) Pol 509, derived from snake venom, was studied directly by analyzing the interactions with synthe tic lipid bilayers using NMR spectroscopy. Functional studies were als o performed by measuring the effects: i), on early biochemical events (adenyl cyclase and phospholipase C activation products), intermediate (surface Ag expression) and late (DNA synthesis) parameters following B-cell activation elicited by PPD-linkage to specific membrane Ig; an d ii), on the presentation of PPD to Ag-specific T-cell lines. Compara tive experiments using PMA and IFN-gamma were also performed. We found that all parameters studied were affected by Pol 509 treatment. In fa ct, while PPD linkage to specific reversed the balance between cAMP an d IP3 existing in unstimulated EBV-B cells, Pol 509 reduced the PPD-in duced accumulation of cAMP to control values and induced a further dec rease of IP3 level. Pol 509-mediated decrease of these second messenge r levels was accompanied by a slight increase of HLA-DR molecule expre ssion and DNA synthesis inhibition. Furthermore, Pol 509 enhanced the efficiency of PPD presentation to T-cell lines. Taken together, these observations suggest that Pol 509, which enhances Ag presentation by m odifying second messenger levels, may be considered as a new immunomod ulatory drug with immunopotentiating activity.