crosspresent

Cross-presentation, sometimes referred to as cross-priming, is the process by which professional antigen-presenting cells capture extracellular or exogenous antigens and present peptide fragments on major histocompatibility complex class I (MHC I) molecules to CD8+ T cells. This contrasts with the conventional MHC I pathway, where endogenous intracellular proteins are processed and presented to cytotoxic T cells. Cross-presentation enables the immune system to activate CD8+ T cells against pathogens or tumor antigens that do not directly infect antigen-presenting cells.

Two main mechanisms have been described. In the cytosolic pathway, internalized antigens escape from endosomes into the cytosol, are degraded by the proteasome, and the resulting peptides are transported by TAP into a compartment where they are loaded onto MHC I. In the vacuolar pathway, processing and loading occur within endosomal or lysosomal compartments with little or no cytosolic proteolysis or TAP involvement. The contribution of each pathway depends on the antigen, the presenting cell, and the uptake route.

Conventional dendritic cells are the most proficient cross-presenters, particularly the CD8α+ subset in mice and BDCA-3+ dendritic cells in humans. Other antigen-presenting cells, such as macrophages and B cells, can cross-present but usually with lower efficiency. Cross-presentation is central to priming naive CD8+ T cells against extracellular viruses, tumor-associated antigens, and certain vaccines, and it may also participate in tolerance under specific conditions.

Understanding cross-presentation informs vaccine design and immunotherapies aimed at enhancing cytotoxic T cell responses. Adjuvants and delivery systems that promote cross-presentation are actively explored to boost anti-tumor and antiviral immunity.