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 synthetic lipid bilayers using NMR spectroscopy. Functional studies were also 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; and ii), on the presentation of PPD to Ag-specific T-cell lines. Comparative experiments using PMA and IFN-gamma were also performed. We found that all parameters studied were affected by Pol 509 treatment. In fact, while PPD linkage to mlg reversed the balance between cAMP and IP3 existing in unstimulated EBV-B cells, Pol 509 reduced the PPD-induced accumulation of cAMP to control values and induced a further decrease of IP3 level. Pol 509-mediated decrease of these second messenger levels was accompanied by a slight increase of HLA-DR molecule expression 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 modifying second messenger levels, may be considered as a new immunomodulatory drug with immunopotentiating activity.
Gilardini Montani
M S
MS
Department of Cellular and Developmental Biology, Univ. La Sapienza, Rome, Italy.
Tuosto
L
L
Delfini
M
M
Guerritore
D
D
Starace
G
G
Politi
E
E
Piccolella
E
E
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1; D008051:Lipid Bilayers / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012910:Snake Venoms / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology; D014373:Tuberculin / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D007295:Inositol Phosphates; D008051:Lipid Bilayers; D009842:Oligopeptides; D012910:Snake Venoms; D014373:Tuberculin; D018799:Intercellular Adhesion Molecule-1; D015060:1,2-Dipalmitoylphosphatidylcholine; D004247:DNA; C081973:pyroglutamyl-leucyl-tryptophan methyl ester; D000242:Cyclic AMP; D011761:Pyrrolidonecarboxylic Acid