title: Identification of the TS2/18-recognized epitope on the CD2 molecule as a target for suppression of T cell cytokine synthesis.
abstract: CD2 mAb can inhibit T cell activation, but the mechanisms involved are still unclear. In this study, we identify the mAb TS2/18, previously reported to bind to an epitope on the distal domain of the CD2 molecule at amino acids 87-99 (1), as a particularly potent inhibitor of T cell cytokine synthesis. Although TS2/18 is comitogenic with the CD2R mAb VIT13, this mAb combination does not induce the secretion of substantial amounts of cytokines. When added to T cells stimulated with the CD2 mAb pair OKT11-VIT13, TS2/18 efficiently blocks the induction of cytokine synthesis induced by that CD2 mAb pair, although it does not interfere with the binding of OKT11. In addition, TS2/18 inhibits the increase in protein tyrosine phosphorylation and the accumulation of phosphatidic acid induced by either OKT11-VIT13 or a cross-linked CD3 mAb. Finally, TS2/18 disrupts CD2 clusters induced by the CD2 mAb pair OKT11-VIT13. We conclude that TS2/18 blocks T cell cytokine synthesis by interfering with early signal transduction, possibly by impairing the formation of signal-transducing molecule complexes on the T cell surface. Together, these data identify the CD2 epitope recognized by the mAb TS2/18 as a candidate epitope for T cell-specific immunosuppressive ligands.
authors.affiliation: Institute of Immunology--VIRCC, Sandoz Research Institute, University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.forename: J
authors.initials: J
authors.lastname: Bohuslav
authors.forename: O
authors.initials: O
authors.lastname: Majdic
authors.forename: H
authors.initials: H
authors.lastname: Stockinger
authors.forename: W
authors.initials: W
authors.lastname: Knapp
authors.forename: W
authors.initials: W
authors.lastname: Holter
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010712:Phosphatidic Acids / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D012397:Rosette Formation; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D017252:CD3 Complex; D016207:Cytokines; D000939:Epitopes; D010712:Phosphatidic Acids; D014443:Tyrosine; D000242:Cyclic AMP; D010770:Phosphotransferases