ANTIBODY LIGATION OF CD7 LEADS TO ASSOCIATION WITH PHOSPHOINOSITIDE 3-KINASE AND PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE FORMATION IN T-LYMPHOCYTES

The CD7 40-kDa glycoprotein is present on a major subset of human T ce lls and in the presence of phorbol esters mediates an accessory pathwa y of T cell activation. Hitherto, the intracellular events elicited by CD7 have been ill-defined. This report demonstrates that cross-linkin g of CD7 results in the formation of phosphatidic acid in the absence of phosphatidylinositol-4,5-bisphosphate metabolism and also the forma tion of D-3 phosphoinositides lipids which have been postulated to act as intracellular regulatory molecules. The magnitude of D-3 phosphoin ositide formation was similar to that induced by CD3. Both the CD7- an d CD3-induced elevation of phosphatidylinositol 3,4,5-trisphosphate ap proximately 5-10 fold less than that elicited by ligation of the costi mulatory molecule CD28 by its counter receptor CD80. The formation of D-3 phosphoinositides following ligation of CD7 coincided with the co- association of CD7 with phosphoinositide 3-kinase, the enzyme which me diates the formation of D-3 phosphoinositide lipids. In contrast, liga tion of another reported T cell accessory molecule CD5, failed to elic it formation of D-3 phosphoinositides, implying that phosphoinositide 3-kinase is not coupled to all T cell molecules with accessory functio ns. Since D-3 phosphoinositides have been suggested to play a pivotal role in T cell costimulatory signals induced by CD28, the results pres ented in this study suggest that CD7 may also influence T cell activat ion via this pathway.