Activation of T cells via CD55: recruitment of early components of the CD3-TCR pathway is required for IL-2 secretion

J Inflamm. 1998;48(1):13-27.

Abstract

It was previously reported that the glycosylphosphatidylinositol (GPI)-anchored CD55 molecule provides a co-stimulatory signal for T lymphocytes and is constitutively associated with the Src-related kinase p56lck. The present studies were undertaken to clarify the mechanism of action of CD55 in T cells. We describe the failure of cross-linking of CD55 alone to induce both the elevation of the intracellular calcium concentration and the tyrosine phosphorylation of PLC-gamma in CD3+ Jurkat cells. By contrast, it is sufficient to induce the phosphorylation of tyrosine residues on p56lck, the TCR-zeta chain as well as ZAP-70. Surprisingly, the observed TCR-zeta and ZAP-70 tyrosine phosphorylations appear delayed compared to stimulation via CD3. Calcium ionophore A23187 in combination with cross-linked CD55 mAb initially caused an acceleration in the kinetic of these two phosphorylation events, followed by IL-2 secretion. Furthermore, transfection of the cytoplasmic domain of TCR-zeta in CD3- Jurkat cells, using a CD16-zeta chimera, demonstrates that CD55-mediated T-cell activation depends on the expression of this chain of the CD3-TCR complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / analysis
  • CD3 Complex / immunology*
  • CD55 Antigens / immunology*
  • Calcium / metabolism
  • Cross-Linking Reagents
  • Cytosol / metabolism
  • Humans
  • Interleukin-2 / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction*
  • T-Lymphocytes / immunology*
  • Transfection
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • Antibodies, Monoclonal
  • CD3 Complex
  • CD55 Antigens
  • Cross-Linking Reagents
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Calcium