either the cytosolic or the vesicular compartments. Top, first panel: viruses and some bacteria replicate in the cytosolic compartment. Their antigens are presented by MHC class I molecules to activate killing by cytotoxic CD8 T cells. Second panel: other bacteria and some parasites are taken up into endosomes, usually by specialized phagocytic cells such as macrophages. Here they are killed and degraded, or in some cases are able to survive and proliferate within the vesicle. Their antigens are presented by MHC class II molecules to activate cytokine production by CD4 T cells. Third panel: proteins derived from extracellular pathogens may bind to cell-surface receptors and enter the vesicular system by endocytosis, illustrated here for antigens bound by the surface immunoglobulin of B cells. These antigens are presented by MHC class II molecules to CD4 helper T cells, which can then stimulate the B cells to produce antibody.
Fig. 6.4 Autophagy pathways can deliver cytosolic antigens for presentation by MHC class II molecules. In the process of autophagy, portions of the cytoplasm are taken into autophagosomes, specialized vesicles that are fused with endocytic vesicles and eventually with lysosomes, where the contents are catabolized. Some of the resulting peptides of this process can be bound to MHC class II molecules and presented on the cell surface. In dendritic cells and macrophages, this can occur in the absence of activation, so that immature dendritic cells may express self peptides in a tolerogenic context, rather than inducing T-cell responses to self antigens.
Fig. 6.3 Cross-presentation of extracellular antigens on MHC class I molecules by dendritic cells. Certain subsets of dendritic cells are efficient in capturing exogenous proteins and loading peptides derived from them onto MHC class I molecules. There is evidence that several cellular pathways may be involved. One route may involve the translocation of ingested proteins from the phagolysosome into the cytosol for degradation by the proteasome, with the resultant peptides then passing through TAP (see Section 6-3) into the endoplasmic reticulum, where they load onto MHC class I molecules in the usual way. Another route may involve direct transport of antigens from the phagolysosome into a vesicular loading compartment—without passage through the cytosol—where peptides are allowed to be bound to mature MHC class I molecules.