Uptake of extracellular virus particles or virus-infected cells into the endocytic pathway by macropinocytosis or phagocytosis can also result in the presentation of viral peptides on MHC class I molecules. This phenomenon, known as cross-presentation, is an alternative to the usual cytosolic pathway for MHC class I antigen processing and is discussed in Section 6-5. Here, viral antigens that enter dendritic cells via endocytic or phagocytic vesicles may be diverted to the cytosol for proteasomal degradation and transferred to the endoplasmic reticulum for loading onto MHC class I molecules. The result is that viruses that do not directly infect dendritic cells can stimulate the activation of CD8 T cells. Cross-presentation is performed most efficiently by a subset of conventional dendritic cells that is specialized for stimulating T-cell responses to intracellular pathogens (see Section 6-5). Any viral infection can therefore lead to the generation of cytotoxic effector CD8 T cells, whether the virus can directly infect dendritic cells or not. In addition, viral peptides presented on the dendritic cell’s MHC class II molecules activate naive CD4 T cells, which leads to the production of effector CD4 T cells that stimulate the production of antiviral antibodies by B cells and produce cytokines that enhance the immune response.
In some cases, such as infections with herpes simplex or influenza viruses, the dendritic cells that migrate to the lymph nodes from peripheral tissues may not be the same cells that finally present antigen to naive T cells. In herpes simplex infection, for example, dendritic cells residing in the skin capture antigen and transport it to the draining lymph nodes (Fig. 9.16). There, some antigen is transferred to resident CD8α-positive dendritic cells, which are the dominant dendritic cells responsible for priming naive CD8 T cells in this infection.
Fig. 9.16 Langerhans cells take up antigen in the skin, migrate differentiate into mature dendritic cells that can no longer ingest to the peripheral lymphoid organs, and present foreign antigen but have co-stimulatory activity. now they can prime both antigens to T cells. Langerhans cells (yellow) are one type of naive Cd8 and Cd4 T cells. In the case of some viral infections, for immature dendritic cell that resides in the epidermis. They ingest example, with herpes simplex virus, some dendritic cells arriving from antigen in various ways but have no co-stimulatory activity (first the site of infection seem able to transfer antigen to resident dendritic panel). In the presence of infection, they take up antigen locally cells (orange) in the lymph nodes (third panel) for presentation of and then migrate to the lymph nodes (second panel). There they class I MhC-restricted antigens to naive Cd8 T cells (fourth panel).
This type of transfer means that antigens from viruses that infect but rapidly kill dendritic cells can still be presented by uninfected dendritic cells that have been activated via their TLRs and can take up the dying dendritic cells and cross-present this material.
cells induces their migration to lymphoid organs and enhances antigen processing.