Identification of the TS2/18-recognized epitope on the CD2 molecule as a target for suppression of T cell cytokine synthesis

J Immunol. 1995 Jun 1;154(11):5813-20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • CD2 Antigens / immunology*
  • CD3 Complex / immunology
  • Cells, Cultured
  • Cyclic AMP / analysis
  • Cytokines / biosynthesis*
  • Epitopes / immunology*
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / immunology
  • Phosphatidic Acids / metabolism
  • Phosphorylation
  • Phosphotransferases / metabolism
  • Rosette Formation
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • Tyrosine / metabolism

Substances

  • Antibodies, Monoclonal
  • CD2 Antigens
  • CD3 Complex
  • Cytokines
  • Epitopes
  • Phosphatidic Acids
  • Tyrosine
  • Cyclic AMP
  • Phosphotransferases