Figure 24–37 Human MHC genes. This simplified schematic drawing shows the location of the genes that encode the transmembrane subunits of class I (light green) and class II (dark green) Mhc proteins. The genes shown encode three types of class I Mhc proteins (hLA-A, hLA-B, and hLA-c) and three types of class II Mhc proteins (hLA-Dp, hLA-DQ, and hLA-Dr). An individual can therefore make six types of class I Mhc proteins (three encoded by maternal genes and three by paternal genes) and more than six types of class II Mhc proteins. Because of the extreme polymorphism of the Mhc genes, the chances are very low that the maternal and paternal alleles will be the same. The number of class II Mhc proteins that can be made is greater than six because there are two DR β genes and because maternally encoded and paternally encoded polypeptide chains can sometimes pair. The entire region shown spans about seven million base pairs and contains other genes that are not shown.
and prevents it from prematurely binding a peptide until the class II MHC protein reaches specialized vesicles, which fuse with endosomes. Here, the invariant chain is removed and peptide fragments (typically 12–20 amino acids long) produced from endocytosed proteins can bind to the groove of the class II MHC proteins, which are then transported to the plasma membrane for display on the surface of the APC. In a healthy host cell, class II MHC protein grooves are loaded with self-peptides derived from normal proteins and will be ignored by T cells because of self-tolerance mechanisms. During an infection, however, pathogen proteins are also endocytosed and processed in the same way, enabling APCs to present pathogen peptides bound to class II MHC proteins to T cells expressing an appropriate TCR (Figure 24–39).
The distinction just discussed between the antigen-processing pathways for loading peptides onto class I and class II MHC proteins is not absolute. Dendritic cells, for example, need to be able to activate cytotoxic T cells to kill virus-infected cells even when the virus does not infect dendritic cells themselves. To do so, specialized subsets of dendritic cells use a process called cross-presentation, which begins when these noninfected dendritic cells phagocytose virus-infected host cells or their fragments. The ingested viral proteins are then released by an unknown mechanism from phagolysosomes into the cytosol, where they are degraded in proteasomes; the resulting protein fragments are then transported into the ER lumen, where they load onto assembling class I MHC proteins. Cross-presentation in dendritic cells is not confined to endocytosed pathogens and their products: it also operates to activate cytotoxic T cells against tumor antigens of cancer cells and the MHC proteins of foreign organ grafts.
Figure 24–38 The processing of an extracellular foreign protein for presentation to cytotoxic T cells. An effector cytotoxic T cell kills a virus-infected cell when it recognizes fragments of an internal viral protein bound to class I Mhc proteins on the surface of the infected cell. Not all viruses enter the cell in the way that this enveloped rNA virus does, but fragments of internal viral proteins always follow the pathway shown. Only a small proportion of the viral proteins synthesized in the cytosol are degraded and transported to the cell surface, but this is sufficient to attract an attack  by a cytotoxic T cell. Several chaperone proteins in the er lumen aid the folding and assembly of class I Mhc proteins (not shown). The assembly  of class I Mhc proteins and their transport to the cell surface require the binding of either a self or foreign peptide (Movie 24.10).