CD50 (INTERCELLULAR-ADHESION MOLECULE-3) STIMULATION INDUCES CALCIUM MOBILIZATION AND TYROSINE PHOSPHORYLATION THROUGH P59(FYN) AND P56(LCK) IN JURKAT T-CELL LINE

The leukocyte differentiation antigen, CD50, has been recently identif ied as the intercellular adhesion molecule 3 (ICAM-3), the third count er-receptor of leukocyte function-associated antigen 1 (LFA-1). This m olecule seems to be specially involved in the adhesion events of the i nitial phases of the immune response. To characterize the role of CD50 in leukocyte interactions, the different molecular events induced aft er cross-linking of CD50 on T cell-derived Jurkat cell line have been analyzed. When cells were incubated with anti-CD50 mAbs and cross-link ed with polyclonal goat anti-mouse immunoglobulins, a rise in intracel lular calcium concentration ([Ca2+](i)) was observed. This increase in [Ca2+](i) was mainly due to the uptake of extracellular Ca2+. This Ca 2+ flux involved tyrosine phosphorylations and was further increased b y CD3 costimulation. These data, together with those obtained by phosp hotyrosine (P-Tyr) immunoprecipitation and in vitro kinase assays, sug gested the involvement of protein-tyrosine kinases (PTK) in CD50 trans duction pathways. By using specific antisera, the presence of p56(lck) and p59(fyn) protein tyrosine kinases (PTK) was clearly demonstrated in the CD50 immunoprecipitates. These findings suggest that the intera ction of CD50 with its natural ligand (LFA-1) may result in T lymphocy te activation events, in which CD50 could play a very active role afte r antigen triggering.