CD8 cells are cross-primed whether antigen is restricted to hematopoietic or nonhematopoietic cells. K^b−/−, actOVA, actOVA.K^b−/−, actOVA.K^b−/−→K^b−/−, and K^b−/−→actOVA.K^b−/− mice were irradiated and reconstituted with 6 × 10⁶ BM cells, 2.4 × 10⁶ CD8 cells, and 10⁵ CD4 cells from C3H.SW mice. (A) Representative flow cytometry from day 13, gated on Ly9.1⁺CD8⁺ cells. (B) Total number of Tet^SIINFEKL+ cells per spleen on days 13 and 35. P = .007, comparing K^b−/− recipients versus actOVA.Kb^−/− recipients. P < .0001, comparing actOVA versus actOVA.K^b−/− mice. P = .05, comparing K^b−/− recipients versus other groups except actOVA recipients (by one-tailed Mann-Whitney). Data from actOVA and actOVA.K^b−/− recipients are combined from 2 experiments with similar results. (C) Percentage of CD8 cells that were Tet^SIINFEKL+ in blood at day 13 (data combined from 3 experiments; P < .0001). Ly9.1⁺CD8⁺ splenocytes from mice transplanted as in panel A produced IFN-γ when restimulated with SIINFEKL at day 13 after BMT.