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 lymphoc ytes and is constitutively associated with the Src-related kinase p56( lck). The present studies were undertaken to clarify the mechanism of action of CD55 in T cells. We describe the failure of crosslinking of CD55 alone to induce both the elevation of the intracellular calcium c oncentration and the tyrosine phosphorylation of PLC-gamma in CD3(+) J urkat cells. By contrast, it is sufficient to induce the phosphorylati on of tyrosine residues on p56(lck), the TCR-zeta chain as well as ZAP -70. Surprisingly, the observed TCR-zeta and ZAP-70 tyrosine phosphory lations appear delayed compared to stimulation via CD3. Calcium ionoph ore A23187 in combination with cross-linked CD55 mAb initially caused an acceleration in the kinetic of these two phosphorylation events, fo llowed 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 expr ession of this chain of the CD3-TCR complex. (C) 1998 Wiley-Liss, Inc.