Enhanced Transmembrane Signalling Activity of Monoclonal Antibody Heteroconjugates Suggests Molecular Interactions between Receptors on the T Cell Surface

摘要

Signal transduction occurs through multiple receptors expressed on mature, resting T cells. In addition to the CD3-T cell receptor complex, the CD2, CD4, CD5, CD7, and CD8 receptors mobilize cytoplasmic calcium within minutes of binding with monoclonal antibodies and additional crosslinking occurs on the cell surface. As an approach to the study the interactions between these receptors and their transduced signals, monoclonal antibodies to each of these receptors were covalently coupled as heteroconjugates and investigated for activity in cytoplasmic calcium mobilization using indo-1 and flow cytometry. Of a total of 35 conjugates studied, there were seven heteroconjugates that showed an increase in activity. Heteroconjugates gained two to three orders of magnitude in titer in calcium mobilization. The increase in activity was not accompanied by an increase in binding titer, indicating that signal transduction occurred at lower levels of receptor occupancy. These results suggest that certain receptors are capable of molecular interactions on the cell surface to form complexes with enhanced activity in signal transduction leading to calcium mobilization. Keywords: Calcium; Cells biology; Membranes biology; Reprints; Monoclonal antibodies. (kt)