IDENTIFICATION OF THE TS2 18-RECOGNIZED EPITOPE ON THE CD2 MOLECULE AS A TARGET FOR SUPPRESSION OF T-CELL CYTOKINE SYNTHESIS/

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 molecul e at amino acids 87-99 (1), as a particularly potent inhibitor of T ce ll cytokine synthesis. Although TS2/18 is comitogenic with the CD2R mA b VIT13, this mAb combination does not induce the secretion of substan tial amounts of cytokines. When added to T cells stimulated with the C D2 mAb pair OKT11-VIT13, TS2/18 efficiently blocks the induction of cy tokine synthesis induced by that CD2 mAb pair, although it does not in terfere with the binding of OKT11. In addition, TS2/18 inhibits the in crease in protein tyrosine phosphorylation and the accumulation of pho sphatidic acid induced by either OKT11-VIT13 or a cross-linked CD3 mAb . Finally, TS2/18 disrupts CD2 clusters induced by the CD2 mAb pair OK T11-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 surf ace. Together, these data identify the CD2 epitope recognized by the m Ab TS2/18 as a candidate epitope for T cell-specific immunosuppressive ligands.