Figure 1. Expression of MHC molecules on mCP-CML and mBC-CML LSCs increases in the alloimmune environment, independently of cognate TCR-MHC interactions.

MHCII expression on WT and MHCII^–/– mBC-CML (A, left) or mCP-CML (A, right) LSCs harvested from mice transplanted with leukemia cells but without GVH-inducing T cells. (B) Irradiated B6 mice were reconstituted with C3H.SW BM and CD4 or CD8 T cells and either mBC-CML or mCP-CML. Mice were sacrificed between days 10 and 14, and LSCs were analyzed for MHCI and MHCII expression. Representative data from at least 3 independent experiments are shown. (C) Irradiated B6 mice were reconstituted with C3H.SW BM with B6 B2m^–/– mBC-CML (MHCI^–) and C3H.SW CD8 cells; B6 MHCII^–/– mBC-CML (MHCII^–) and C3H.SW CD4 cells; or WT B6 mBC-CML and C3H.SW CD4 or CD8 cells. On day 15 after BMT, splenocytes were harvested, and MHCI and MHCII expression on mBC-CML LSCs was assessed. Similar MHC upregulation was noted on LSCs harvested from BM (data not shown). Data are representative of 3 independent experiments. (D) Mice were transplanted as in C, except with B2m^–/– or MHCII^–/– mCP-CML cells. MHC upregulation was also independent of TCR-MHC interactions. (E) Irradiated BALB/c mice were reconstituted with B6 BM and B6 mCP-CML with no T cells or with B6 CD4 or CD8 cells. MHCII and MHCI were upregulated on splenic mCP-CML LSCs on day 15 after BMT. Similar MHC upregulation was seen in BM LSCs (data not shown). (F) MHCII^hi and MHCII^lo mBC-CML LSCs from mice undergoing a GVHD response (C3H.SW→B6 model with GVH induced by CD4 cells) were sort purified and transferred into sublethally irradiated B6 mice. Both populations transferred disease (F, left panels). Progeny of sorted MHCII^hi and MHCII^lo mBC-CML cells recovered 15 days after transfer were MHCII^lo (F, right panel). FMO, fluorescence minus one.