Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8<sup>+</sup> T cells into activated cytotoxic CD8<sup>+</sup> T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.
Cross-presentation is of particular importance, because it permits the presentation of exogenous antigens, which are normally presented by MHC II on the surface of dendritic cells, to also be presented through the MHC I pathway. The MHC I pathway is normally used to present endogenous antigens that have infected a particular cell. However, cross presenting cells are able to utilize the MHC I pathway to present exogenous antigens (ones not from the cell itself) to trigger an adaptive immune response by activating cytotoxic CD8+ T cells recognizing the exogenous antigens on the MHC class I complexes.
History
The first evidence of cross-presentation was reported in 1976 by Michael J. Bevan after injection of grafted cells carrying foreign minor histocompatibility (MiHA) molecules. This resulted in a CD8+ T cell response induced by antigen-presenting cells of the recipient against the foreign MiHA cells. Because of this, Bevan implied that these antigen presenting cells must have engulfed and cross presented these foreign MiHA cells to host cytotoxic CD8+ cells, thus triggering an adaptive immune response against the grafted tissue. This observation was termed "cross-priming".
Cross-presenting cells
The primary and most efficient cross-presenting cells are dendritic cells, though macrophages, B lymphocytes and sinusoidal endothelial cells have also been observed to cross present antigens in vivo and in vitro. However, in vivo dendritic cells have been found to be the most efficient and common antigen presenting cells to cross present antigens in MHC I molecules. mDCs are categorized as migratory DCs, resident DCs, Langerhans cells, and inflammatory dendritic cells. All mDCs have specialized functions and secretory factors, but they are all still able to cross present antigens in order to activate cytotoxic CD8+ T cells.
Vacuolar and cytosolic diversion
In addition to solid structure uptake, dendritic cell phagocytosis simultaneously modifies the kinetics of endosomal trafficking and maturation. As a consequence, external soluble antigens are targeted into the MHC class I cross-presentation pathway instead of the MHC Class II pathway. However, there is still uncertainty in regard to a mechanistic pathway for cross presentation within an antigen presenting cell. Currently, there are two main pathways proposed, cytosolic and vacuolar. or back into the same endosome for loading onto MHC class I complexes,. It is believed that MHC I loading occurs both in the ER as well as phagocytic vesicles such as an endosome in the cytosolic pathway. Even though many viruses can inhibit and degrade dendritic cell activity, cross-presenting dendritic cells that are unaffected by the virus are able to intake the infected peripheral cell and still cross present the exogenous antigen to cytotoxic T cells. The action of cross priming can bolster immunity against antigens that target intracellular peripheral tissues that are unable to be mediated by antibodies produced through B cells.