IFN-α/β, and not IFN-γ signaling, is critical for spontaneous CD8⁺ T cell priming to tumor-associated antigens. (A and B) Wild-type, IFN-α/βR^−/−, or IFN-α/βR^−/−/IFN-γR^−/− mice were inoculated s.c. with 10⁶ B16.SIY tumor cells. Splenocytes were harvested 17 d later and restimulated for 16 h in the presence or absence of or soluble SIY peptide (A). The frequency of tumor-specific IFN-γ–producing cells was assessed by ELISPOT. ***, P < 0.0001 versus WT. (B) cells were gated on CD8⁺CD4⁻B220⁻ and the frequency of SIY-specific CD8⁺ T cells was assessed by FACS using specific tetramers. ***, P < 0.0009; **, P < 0.0027 versus WT. (C) Wild-type and IFN-γR^−/− mice were inoculated s.c. with 10⁶ B16.SIY tumor cells, and splenocytes were harvested 17 d later and restimulated for 16 h in the presence or absence of soluble SIY peptide, and then the frequency of tumor-specific IFN-γ–producing cells was assessed by ELISPOT. P = 0.268 versus WT. (D and E) Wild-type and Stat1^−/− mice were inoculated s.c. with 10⁶ B16.SIY tumor cells, and splenocytes were harvested 17 d later and restimulated for 16 h in the presence or absence of soluble SIY peptide (D). The frequency of tumor-specific IFN-γ–producing cells was assessed by ELISPOT. ***, P < 0.0001 versus WT. (E) cells were gated on CD8⁺CD4⁻B220⁻, and the frequency of SIY-specific CD8⁺ T cells was assessed by FACS using specific tetramers. **, P = 0.0029 versus WT. Data represent mean ± SEM (n = 5), and are representative of three independent experiments.