Pospori and colleagues retrovirally transduced enriched murine HSCs with human TCRs recognizing antigens in the context of HLA-A2. These cells were then transplanted into irradiated recipients expressing human HLA-A2 as a transgene resulting in positive selection without deletion and export of human TCR-bearing T cells to the periphery. T cells recognizing WT1 expressed activation markers and were functional without vaccination. This did not occur with nonself-antigen–recognizing T cells. Professional illustration by Debra T. Dartez.