We have recently described the
A6H antigen as a novel 120-140 kDa molecule which is co-expressed on human peripheral blood T cells and
renal cell carcinoma cells. Engagement of the
A6H antigen results in co-stimulation of CD4+ T cells but it remained unknown how cross-talk between the
A6H antigen and the
TCR-CD3 complex takes place and which signaling pathway might be involved. Here we show that
ligation of the
A6H antigen with mAb induces
tyrosine phosphorylation of the Lck
protein tyrosine kinase (PTK). Co-
ligation of the
A6H antigen with CD3 resulted in augmented Lck phosphorylation and mitogenesis. In addition, A6H
ligation induced an up-regulation of CD3-mediated phosphorylation of the 23 kDa high mol. wt form of TCR zeta and the zeta-associated
protein, ZAP-70. Co-precipitation of Lck and ZAP-70 was only seen in T cells activated by combined A6H and anti-CD3 stimulation. In contrast, another Src family PTK, Fyn, was not affected by A6H
ligation. In conclusion, we now demonstrate, for the first time, that A6H
ligation triggers Lck phosphorylation, and that cross-talk between A6H and the
TCR-CD3 complex involves Lck, ZAP-70 and the slow migrating
isoform of TCR zeta. These results further suggests that A6H
ligation is sufficient for triggering some of the early events in T cell activation, whereas full activation of the T cell, characterized by proliferation and
cytokine production, requires co-
ligation of the
TCR-CD3 complex.