MOLECULAR-CLONING AND EXPRESSION OF EARLY T-CELL COSTIMULATORY MOLECULE-1 AND ITS CHARACTERIZATION AS B7-2 MOLECULE

The interaction of T cell CD28/CTLA-4 receptors with B7-1 activation A g on APC represents an important costimulatory pathway in T cell activ ation. However, it is now evident that this costimulatory pathway is n either unique nor universal for the activation of T cells. Our previou s study indicated that a 60-kDa membrane protein, recognized by mAb 2D 10, was expressed before B7 by activated murine B cells. This molecule was critically involved in activation of T cells in response to auto- and alloantigens. In the present study, we report on the isolation of a cDNA for this early T cell costimulatory molecule (ETC-1). ETC-1, l ike B7-1, is a member of the Ig supergene family and is composed of 30 3 amino acids. Nucleic acid sequence comparison indicated that ETC-1 i s identical to the B7-2 molecule. When expressed in Chinese hamster ov ary cells, ETC-1 showed profound T cell costimulatory activity as demo nstrated by its ability to enhance CD4 T cell proliferation in respons e to Con A or anti-CD3 stimulation. Furthermore, ETC-1 also bound to b oth CD28-Ig and CTLA4-Ig fusion proteins. These results strongly suppo rt the notion that the interaction of ETC-1/B7-2 with CD28 or CTLA-4 r eceptors represents an alternative T cell costimulatory pathway.