Adaptive antiviral immunity begins with antigen presentation, and the pathway a viral peptide takes determines which T cell sees it. Peptides derived from proteins in the cytosol are degraded by the proteasome, transported into the endoplasmic reticulum by TAP, loaded onto MHC class I, and displayed at the cell surface. Because viral replication generates cytosolic proteins, infected cells display viral peptides on MHC class I and become visible to CD8+ cytotoxic T cells. CD8+ T cells whose T cell receptor (TCR) matches the peptide-MHC complex are activated, proliferate, and kill the presenting cell by releasing perforin and granzymes and by engaging Fas.
A second route handles extracellular antigen. Dendritic cells engulf viral particles or debris, degrade them in endosomes and lysosomes, and load the resulting peptides onto MHC class II. These complexes are recognized by CD4+ T cells, which do not kill the presenting cell directly but instead provide help. Cross-presentation allows dendritic cells to route engulfed antigen onto MHC class I as well, which is important because it lets a dendritic cell prime CD8+ T cells without being infected itself.
The division of labor matters: MHC class I reports what is being made inside a cell, while MHC class II reports what has been taken up from outside. A virus that replicates in the cytosol is therefore detected by CD8+ T cells, whereas the same virus encountered as a particle by a dendritic cell drives CD4+ T cell activation.