Using heterologous prime-boost (DNA immunization followed by immunization with transfected cells), we have generated depleting mouse anti-baboon CD2 monoclonal antibodies (mAb). These anti-CD2 mAb recognized a diverse range of primate CD2 from New World monkeys and Old World monkeys to humans and have potent immunosuppressive activity for human allo-MLR responses and anti-tetanus-toxoid recall responses. There was no upregulation of activation markers or release of cytokines when the mAb were incubated with human peripheral blood mononuclear cells. Using chimeric NOD-SCID IL2rγnull mice, the mAb were shown to deplete human and cynomolgus monkey T cells in vivo. These anti-CD2 mAb may therefore be important immunological tools in allo- and xenotransplantation. ; Jamie L. Brady, Stuart I. Mannering, Svjetlana Kireta, Patrick T. Coates, Anna I. Proietto, Peter J. Cowan, Anthony J. F. D'Apice and Andrew M. Lew ; © 2009 Australasian Society for Immunology Inc. All rights reserved.