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Keywords:

  • Comparative immunology/evolution;
  • Tumor immunity;
  • Xenopus;
  • NK cells;
  • CTL

Abstract

In Xenopus as in mammals, gp96 stimulates MHC-restricted cellular immunity against chaperoned minor histocompatibility (H) antigens (Ag). In adult Xenopus, gp96 also elicits peptide-specific effectors against MHC class Ia-negative 15/0 tumors. To determine whether gp96 can generate functionally heterogeneous CD8+ effectors (CTL that kill MHC class Ia+ minor H-Ag-disparate lymphoblasts and MHC class Ia tumor targets), LG-6 isogenetic frogs were immunized with gp96 purified either from MHC-identical but minor H-Ag-disparate LG-15 normal tissues or from the MHC class Ia-negative 15/0 tumor line (derived from LG-15 frogs). LG-15 normal liver-derived gp96 did not induce detectable CD8+in vitro killing against 15/0 tumor cells. However, 15/0-derived gp96 did induce killing against both MHC class Ia+ LG-15 lymphoblasts and the MHC class Ia 15/0 tumor, but not against another MHC class Ia tumor (B3B7) or against LG-6 lymphoblasts. Tumor killing was better when 15/0 rather than normal LG-15 irradiated stimulators were used, but in vitro stimulation without prior in vivo immunization was ineffective. These data suggest that (1) 15/0-derived gp96 chaperones minor H-Ag shared with normal LG-15 lymphocytes and elicits MHC-restricted CTL, and (2) 15/0-derived gp96, but not normal liver-derived gp96, generates CD8+ effectors that kill 15/0 tumor cells in the absence of MHC class Ia expression.