Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis.
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.
PubMed ID: 23390375
PMC ID: PMC3559192
Grant support: 1R03-HD061671-01 NICHD NIH HHS , R24 AI059830 NIAID NIH HHS , R24-AI-059830-06 NIAID NIH HHS , T32-AI 07285 NIAID NIH HHS
Genes referenced: ag1 apcs.2 hsp70 hsp90b1 hspa1a hspa1l myh4 myh6