Phylogenetic conservation of gp96-mediated antigen-specific cellular immunity: new evidence from adoptive cell transfer in xenopus.

BACKGROUND:In vertebrates from man to frogs, the heat shock protein (hsp) gp96 elicits T-cell responses against antigenic peptides that it chaperones. In Xenopus, immunization with gp96 purified from normal tissues accelerates rejection of MHC identical, minor histocompatibility (H) antigen-disparate skin grafts in vivo and induces MHC-restricted CTL responses in vitro. Also in Xenopus, gp96 derived from MHC class I-negative tumors elicits peptide-specific responses against these tumors in vivo and MHC-unrestricted CD8 killing in vitro. We have developed an adoptive cell transfer protocol to further characterize these gp96-stimulated Xenopus effectors in vivo. METHODS AND RESULTS:Carboxyfluorescein diacetate succinimidyl ester (CFSE)-stained splenocytes from cloned LG-6 donor frogs immunized with gp96 purified from minor H-antigen-disparate LG-15 tissues were transferred into LG-6 recipients bearing a LG-15 minor H antigen (ag)-disparate skin graft. Primed anti-LG-15 but not naive CFSE T cells accumulated and divided in the spleen of allografted recipients to a greater extent than in those of autografted recipients. Similar accumulation and division occurred when CD8 T cells primed by 15/0 tumor-derived gp96 were transferred to an isogeneic recipient bearing the same MHC class I-negative tumor. Furthermore, the transfer of such primed antitumor splenocytes into naive recipients before tumor challenge delayed the appearance of tumors. CONCLUSIONS:These data provide new in vivo evidence that in frogs as in mammals, gp96 can prime CD8 T cells against antigens they chaperone. In addition, at least in Xenopus, gp96 can prime CD8(+) T-cell effectors that are not MHC restricted.

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