title: Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis.
abstract: The heat shock proteins (HSPs) gp96 and HSP70 mediate potent antigen-dependent anti-tumor T cell responses in both mammals and Xenopus laevis. We have shown that frogs immunized with total HSP70 generate CD8+ T cell responses against the Xenopus thymic lymphoid tumor 15/0 that expresses several non-classical MHC class Ib (class Ib) genes, but no classical MHC class Ia (class Ia). In the absence of class Ia, we hypothesized that hsp72 can prime class Ib-mediated anti-tumor unconventional CD8+ T cells in an antigen-dependent manner. To test this, we produced Xenopus recombinant HSP70 proteins (both the cognate hsc73 and the inducible hsp72) from stable 15/0 tumor transfectants. We used an in vivo cross-presentation assay to prime animals by adoptive transfer of HSP-pulsed antigen-presenting cells (APCs) and showed that both hsp72-and hsc73-Ag complexes have a similar potential to elicit class Ia-mediated T cell responses against minor histocompatibility (H) Ag skin grafts. In contrast, our in vivo cross-presentation assay revealed that hsp72 was more potent than hsc73 in generating protective immune responses against the class Ia-negative 15/0 tumors in an Ag-dependent and class Ib-mediated manner. These results suggest that hsp72 can stimulate class Ib-mediated immune responses and represents a promising candidate for immunotherapy against malignancies with downregulated class Ia expression.
authors: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors: Hristina
authors: H
authors: Nedelkovska
authors: Jacques
authors: J
authors: Robert
mesh_terms: D000818:Animals; D045142:Cross-Priming / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D050883:HSC70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007109:Immunity / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000302:isolation & purification; D016038:Skin Transplantation / Q000276:immunology; D029867:Xenopus Proteins / Q000276:immunology / Q000378:metabolism; D014982:Xenopus laevis / Q000276:immunology* / Q000378:metabolism
chemical_list: D050883:HSC70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D029867:Xenopus Proteins
keywords: Xenopus laevis; comparative immunology; heat shock proteins; tumor immunity
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