Figure 2.

Antigen internalization, processing and presentation. (A) Exogenous proteins. DCs use three major ways to internalize exogenous antigens: (1) receptor-mediated endocytosis; (2) phagocytosis; (3) micropinocytosis. Exogenous antigens are delivered from early endosomes to late endosomes/endolysosomes, where they are degraded into peptides. These high-affinity peptides bind to MHC-II molecules, and the peptide-MHC-II complex are transported to the plasma membrane through the tubules and vesicles derived from the endosome. (B) Endogenous proteins. Cytosolic proteins first undergo proteolysis, then the peptides are translocated into the ER through TAP proteins. ERAP1/2 in the ER lumen further digests the peptides to fit the MHC-I. Finally, peptide-MHC-I complex are transported to the plasma membrane through classical secretion. (C) Antigen cross-presentation. Exogenous antigens can be presented on MHC-I molecules through two pathways: the vacuolar and cytosolic pathway. In the vacuolar pathway, engulfed antigens are digested into peptides in phagosomes, where MHC-I molecules bind to the peptides. In the cytosolic pathway, antigens first enter the cytosol and are degraded into peptides by proteasome. Peptides are transported into endosome or ER through TAP, and further trimmed by IRAP or ERAP, respectively. Trimmed peptides bind to MHC-I and the complex are transported to the plasma membrane.