Minor histocompatibility antigen-specific MHC-restricted CD8 T cell responses elicited by heat shock proteins.
In mammals, the heat shock proteins (HSP) gp96 and hsp70 elicit potent specific MHC class I-restricted CD8(+) T cell (CTL) response to exogenous peptides they chaperone. We show in this study that in the adult frog Xenopus, a species whose common ancestors with mammals date back 300 million years, both hsp70 and gp96 generate an adaptive specific cellular immune response against chaperoned minor histocompatibility antigenic peptides that effects an accelerated rejection of minor histocompatibility-locus disparate skin grafts in vivo and an MHC-specific CD8(+) cytotoxic T cell response in vitro. In naturally class I-deficient but immunocompetent Xenopus larvae, gp96 also generates an antitumor immune response that is independent of chaperoned peptides (i.e., gp96 purified from normal tissue also generates a significant antitumor response); this suggests a prominent contribution of an innate type of response in the absence of MHC class I Ags.
Robert
Jacques
J
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. robert@uhura.rochester.edu
Gantress
Jennifer
J
Rau
Laura
L
Bell
Alisa
A
Cohen
Nicholas
N
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000502:physiology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007114:Immunization; D007814:Larva / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000502:physiology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology; D010455:Peptides / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014981:Xenopus; D029867:Xenopus Proteins / Q000008:administration & dosage / Q000502:physiology
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D029867:Xenopus Proteins; C052646:sarcoma glycoprotein gp96 rejection antigens