Phylogenetic conservation of the molecular and immunological   properties of the chaperones gp96 and hsp70.
The heat shock proteins (HSP) gp96 and hsp70 have been shown to have a critical role in eliciting adaptive immune responses to cancers and viruses. This role derives from (i) their ability to chaperone antigenic peptides generated in the cells from which the HSP are isolated, and (ii) their capacity to interact with antigen presenting cells (APC) which re-present the HSP-chaperoned peptides in context of MHC I molecules. We have asked whether the immunological properties of HSP extend beyond the mammals to other phyla. We report here the serological, biochemical, genetic, and immunological characterization of the Xenopus gp96. Like mammalian gp96, Xenopus gp96 forms non-covalent complexes with peptides. Immunization with gp96 and hsp70 purified from Xenopus tumors, elicits potent and specific anti-tumor immunity, which is dependent on their ability to chaperone peptides in vivo. An immunogenic peptide chaperoned by the Xenopus gp96 can be processed and presented by mouse APC, to antigen-specific CD8+ T cells of mice. The remarkable conservation of these essential immunological properties of gp96 and hsp70 between amphibians and mammals suggests the importance of HSP in the evolution of the vertebrate immune system.
University of Rochester Medical Center, Rochester, USA.
J
J
Robert
A
A
Ménoret
S
S
Basu
N
N
Cohen
P R
PR
Srivastava
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014981:Xenopus
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C052646:sarcoma glycoprotein gp96 rejection antigens