Cancer Immunity 2:16 (2002)

Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity

Robert J. Binder, Sumeet K. Kumar, and Pramod K. Srivastava

Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT

Keywords: mice, immunization, alpha2-macroglobulin, heat shock proteins, peptides, tumor immunity

Abstract

Immunization of mice with in vitro reconstituted alpha2-macroglobulin-peptide complexes primes peptide-specific CTL responses. We show here using the H-Y antigenic system that naturally produced, immunogenic alpha2-macroglobulin-peptide complexes can be isolated from the sera of normal male mice. As an application of these ideas to cancer immunity, we show that the immunity evoked by alpha2-macroglobulin-peptide complexes reconstituted in vitro is effective in prophylaxis against tumors. Furthermore, complex peptide mixtures isolated from tumor lysates can be reconstituted non-covalently with alpha2-macroglobulin and such complexes elicit potent protective tumor immunity. This approach circumvents the need for prior knowledge of the identity of the immunogenic peptides. The heat shock protein/alpha2-macroglobulin receptor CD91 is shown to be involved in the ability of heat shock proteins or alpha2-macroglobulin to elicit an anti-tumor immune response.