Isoforms of human B7-H3 co-signalling molecule for T cell activation as potential immunoregulatory agents.

B7 family molecules, which are expressed on antigen-presenting cells and display extracellular regions containing immunoglobulin (Ig) variable (V)- and constant (C)-like domains, are known to modulate T cell receptor (TCR)-mediated T cell activation by providing co-signals that are either stimulatory or inhibitory. One of the most recently identified members of this family is B7-H3 (B7 homologue 3). Here, evidence is presented that human B7-H3 exists as two isoforms: B7-H3 VC, which contains one IgV- and IgC-like domain, and B7-H3 VCVC, which contains two such domains. The latter represents the predominant B7-H3 molecule detectable in various human tissues. Both B7-H3 isoforms are shown to decrease the proliferation and cytokine production induced by TCR activation of human T cells in vitro. It is therefore claimed that B7-H3 molecules may provide tools to modulate immune responses for therapeutic purpose.