Activation of T cells via CD55: recruitment of early components of the CD3-TCR pathway is required for IL-2 secretion.
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.
Tosello
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AC
Institut National de la Santé et de la Recherche Médicale INSERM U343, Hôpital de l'Archet, Nice, France.
Mary
F
F
Amiot
M
M
Bernard
A
A
Mary
D
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology*; D018958:CD55 Antigens / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D018958:CD55 Antigens; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D002118:Calcium