CD8+ T cells can recognise and kill virus-infected cells and cancer cells. Understanding how they first recognise antigen, then proliferate and differentiate, is crucial to improving the design of vaccines and immunotherapy for viral infections and cancer. The immunology canon teaches us that a subset of dendritic cells (CLEC9A+ XCR1+ “DC1”) initiates CD8+ T cell responses in lymph nodes. However single cell and spatial data from human lymphoid tissue suggest DC1 are unlikely to fulfil this role in humans. What are the alternative scenarios for “priming” human CD8+ T cells – and what are the implications for immune therapy?