Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity.
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.
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.
Robert J
RJ
Binder
Sumeet K
SK
Kumar
Pramod K
PK
Srivastava
D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism; D007111:Immunity, Cellular; D007114:Immunization; D007167:Immunotherapy; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000511:alpha-Macroglobulins / Q000276:immunology* / Q000378:metabolism
D006360:Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D000511:alpha-Macroglobulins