The study by den Haan et al. investigates the role of dendritic cells (DCs) in cross-priming, a process where antigen-presenting cells (APCs) present cell-associated antigens to CD8+ T cells. The authors used β2-microglobulin-deficient splenocytes loaded with ovalbumin (OVA) to prime mice, and then isolated and analyzed splenic DCs to determine their ability to present OVA. They found that only CD8+ DCs, not CD8- DCs, were capable of cross-presenting OVA to CD8+ T cells. This cross-presentation was dependent on the transporter associated with antigen presentation (TAP), suggesting an endosome-to-cytosol transport pathway. Further analysis revealed that only lymphoid DCs, characterized by low expression of CD11b and high expression of CD11c, were capable of cross-presenting OVA. Depletion experiments confirmed that CD8+ lymphoid DCs were the primary APCs responsible for cross-presenting OVA. The authors concluded that CD8+ lymphoid DCs play a crucial role in generating cytotoxic T lymphocyte responses specific for cell-associated antigens.The study by den Haan et al. investigates the role of dendritic cells (DCs) in cross-priming, a process where antigen-presenting cells (APCs) present cell-associated antigens to CD8+ T cells. The authors used β2-microglobulin-deficient splenocytes loaded with ovalbumin (OVA) to prime mice, and then isolated and analyzed splenic DCs to determine their ability to present OVA. They found that only CD8+ DCs, not CD8- DCs, were capable of cross-presenting OVA to CD8+ T cells. This cross-presentation was dependent on the transporter associated with antigen presentation (TAP), suggesting an endosome-to-cytosol transport pathway. Further analysis revealed that only lymphoid DCs, characterized by low expression of CD11b and high expression of CD11c, were capable of cross-presenting OVA. Depletion experiments confirmed that CD8+ lymphoid DCs were the primary APCs responsible for cross-presenting OVA. The authors concluded that CD8+ lymphoid DCs play a crucial role in generating cytotoxic T lymphocyte responses specific for cell-associated antigens.