Fig. 2.

DNA- and amino acid-based antigen internalization and processing. Please note that certain cellular processes shown are generally for somatic cells, while others are for antigen presenting cells (APCs). (1) endocytosis; (2) extracellular activation through TLR2/4 resulting in the expression of proinflammatory cytokines and chemokines (IL-8/10, TNFα); (3) proton sponge effect for DNA vaccines (4) CpG sequences activating TLR9 and resulting in IL-4 and IFNα release; (5) cytosolic degradation pathway resulting in (6) MHC II antigen presentation to CD4⁺ T cells; (7) proteasome degradation pathway and the eventual MHC I antigen presentation to CD8⁺ T cells. Direct somatic cell engulfment/APC display entails (1, 5, 3), leading to MHC II-peptide display. Steps for phagocytosis of a transfected (nonviral) or transformed (viral) cell/cross-priming entails (1, 4, 6), leading to MHC 1-peptide display. Steps for Toll-like receptor (TLR) activation entails (2, 7). (APC, antigen-presenting cell; CCR5, C–C chemokine receptor type 5; CpG DNA, DNA fragment containing cytosine nucleotide followed by guanine nucleotide; ER, endoplasmic reticulum; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; TNF, tumor necrosis factor; TLR, Toll-like receptor; VLP, virus-like particle).