Antigen processing-Cross presentation

MHC class I molecules generally present peptide antigens derived from proteins synthesized by the cell itself to CD8+ T cells. However, in some circumstances, antigens from extracellular environment can be presented on MHC class I to stimulate CD8+ T cell immunity, a process termed cross-presentation (Rock & Shen. 2005). Cross-presentation/cross-priming is the ability of antigen presenting cells (APCs) to present exogenous antigens on MHC class I molecules to CD8+ T lymphocytes. Among all the APCs, dendritic cells (DC) are the dominant antigen cross presenting cell types in vivo, although macrophages and B cells appear to cross present model antigens in vitro with a low degree of efficiency (Amigorena & Savina. 2010, Ackermann & Peter Cresswell. 2004). Compared to macrophages, DCs have low levels of lysosomal proteases and exhibit limited lysosomal degradation. This limited proteolysis of internalized antigens by DCs might contribute to their high efficiency for cross-presentation (Monua & Trombetta. 2007). APCs acquire the exogenous antigens through endocytic mechanisms, especially phagosomes for particulate/cell-associated antigens and endosomes for soluble protein antigens. There does not seem to be a unique pathway for cross-presentation but rather different potential mechanisms of cross-presentation have been proposed. These proposed pathways can be classified according to the location where two key events occur: 1) processing of the antigenic protein and 2) loading of the processed peptide on to MHC I molecule (Blanchard & Shastri. 2010). Based on the requirement for TAP and cytosolic proteases two mechanisms have been described, a cytosolic pathway (TAP-dependent and proteasome-dependent) or a vacuolar pathway (TAP- and proteasome-independent) (Blanchard & Shastri. 2010, Amigorena & Savina. 2010). Regarding peptide-loading, MHC I could be loaded in the ER or in the phagosome and recycled to cell surface (Blanchard & Shastri. 2010). Exogenous soluble antigens are cross-presented by dendritic cells, albeit with lower efficiency than for particulate substrates. Soluble antigens destined for cross-presentation are taken up by distinct endocytosis mechanisms which route them into stable early endosomes and then to the cytoplasm for proteasomal degradation and peptide loading. The outcome of the cross-presentation can be either tolerance or immunity (Rock & Shen. 2005).

Summary from Reactome (R-HSA-1236975), read 2026-09-23.