gamma-glutamyl transpeptidase, an ecto-enzyme regulator of intracellular redox potential, is a component of TM4 signal transduction complexes

CD21 (C3dg/EBV receptor) is physically associated on B cells with a complex of proteins that includes CD19 and the widely distributed tetraspan 4 (TM4 ) family protein CD81 as well as other TM4 proteins (CD53, CD37 and CD82). Monoclonal antibodies (mAb) were generated that blocked homotypic adhesion induced by CD21 ligands in the human B cell line Balm-1. One inhibitory mAb (3A8) was found to recognize the ecto-enzyme gamma-glutamyl transpeptidase (GGT), a membrane protein involved in recycling extracellular glutathione and regulating intracellular redox potential. Molecular associations betwee n GGT and TM4 proteins CD81, CD53 and CD82, in addition to CD21 and CD19, w ere detected by cc-precipitation and co-capping analysis. GGT is expressed on several B and T cell lines independently of CD21 expression. These resul ts demonstrate that GGT is a component of widely distributed TM4 complexes, and that on B cells the GGT-containing TM4 complexes also contain CD19 and CD21.