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 cells and in the presence of phorbol esters mediates an accessory pathway of T cell activation. Hitherto, the intracellular events elicited by CD7 have been ill-defined. This report demonstrates that cross-linking of CD7 results in the formation of phosphatidic acid in the absence of phosphatidylinositol-4,5-bisphosphate metabolism and also the formation of D-3 phosphoinositides lipids which have been postulated to act as intracellular regulatory molecules. The magnitude of D-3 phosphoinositide formation was similar to that induced by CD3. Both the CD7- and CD3-induced elevation of phosphatidylinositol 3,4,5-trisphosphate approximately 5-10 fold less than that elicited by ligation of the costimulatory 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 mediates the formation of D-3 phosphoinositide lipids. In contrast, ligation of another reported T cell accessory molecule CD5, failed to elicit formation of D-3 phosphoinositides, implying that phosphoinositide 3-kinase is not coupled to all T cell molecules with accessory functions. Since D-3 phosphoinositides have been suggested to play a pivotal role in T cell costimulatory signals induced by CD28, the results presented in this study suggest that CD7 may also influence T cell activation via this pathway.