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Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular 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.
AuthorsRobert J Binder, Sumeet K Kumar, Pramod K Srivastava
JournalCancer immunity (Cancer Immun) Vol. 2 Pg. 16 (Dec 18 2002) ISSN: 1424-9634 [Electronic] United States
PMID12747761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Heat-Shock Proteins
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Peptides
  • alpha-Macroglobulins
Topics
  • Animals
  • Heat-Shock Proteins (metabolism)
  • Immunity, Cellular
  • Immunization
  • Immunotherapy
  • Low Density Lipoprotein Receptor-Related Protein-1 (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental (prevention & control)
  • Peptides (immunology, metabolism)
  • T-Lymphocytes, Cytotoxic (immunology)
  • alpha-Macroglobulins (immunology, metabolism)

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