Establishment and characterization of a novel anti-DNAM-1 monoclonal antibody.

DNAM-1 (CD226) is expressed on the majority of NK cells, CD8(+) T cells, and CD4(+) T cells and mediates an activating signal in these cells upon binding to the ligands CD155 or CD112 expressed on target cells or antigen-presenting cells. DNAM-1 plays an important role in tumor immunity mediated by NK cells and CD8(+) T cells and the development of graft-versus-host disease (GVHD) in mice. We previously generated a monoclonal antibody against mouse DNAM-1, TX42, which inhibited DNAM-1 binding to its ligands CD155 and CD112 and inhibited activation of NK cells and CD8(+) T cells in vitro. Injection of mice with TX42 ameliorated the development of GVHD in mice. Here, we generated a new clone of anti-DNAM-1 MAb, TX92. TX92 similarly stained primary spleen cells, including CD8(+) and CD4(+) T cells and NK cells. TX92 as well as TX42 interfered with the interaction between DNAM-1 and ligands CD155 and CD112. However, TX92 recognizes a different epitope and, unlike TX42 partially, but not completely, depleted peripheral blood (PB) CD8(+) T cells in vivo. Thus, TX92 is a unique MAb that is characterized not only by inhibitory function of DNAM-1 binding to the ligands but also by function of partial depletion of PB CD8(+) T cells.