Antigen Processing and Presentation
Peptides are processed and presented by two classical pathways:
- In MHC class II phagocytes such as macrophages and immature dendritic cells uptake entities by phagocytosis into phagosomes—though B cells exhibit the more general endocytosis into endosomes—which fuse with lysosomes whose acidic enzymes cleave the uptaken protein into many different peptides. Via physicochemical dynamics in molecular interaction with the particular MHC class II variants borne by the host, encoded in the host's genome, a particular peptide exhibits immunodominance and loads onto MHC class II molecules. These are trafficked to and externalized on the cell surface.
- In MHC class I any nucleated cell normally presents cytosolic peptides, mostly self peptides derived from protein turnover and defective ribosomal products. During viral infection, intracellular microorganism infection, or cancerous transformation, such proteins degraded in the proteosome are as well loaded onto MHC class I molecules and displayed on the cell surface. T lymphocytes can detect a peptide displayed at 0.1%-1% of the MHC molecules.
| Characteristic | MHC-I pathway | MHC-II pathway |
|---|---|---|
| Composition of the stable peptide-MHC complex | Polymorphic chain α and β2 microglobulin, peptide bound to α chain | Polymorphic chains α and β, peptide binds to both |
| Types of antigen presenting cells (APC) | All nucleated cells | Dendritic cells, mononuclear phagocytes, B lymphocytes, some endothelial cells, epithelium of thymus |
| T lymphocytes able to respond | Cytotoxic T lymphocytes (CD8+) | Helper T lymphocytes (CD4+) |
| Origin of antigenic proteins | cytosolic proteins (mostly synthetized by the cell; may also enter from the extracellular medium via phagosomes) | Proteins present in endosomes or lysosomes (mostly internalized from extracellular medium) |
| Enzymes responsible for peptide generation | Cytosolic proteasome | Proteases from endosomes and lysosomes (for instance, cathepsin) |
| Location of loading the peptide on the MHC molecule | Endoplasmic reticulum | Specialized vesicular compartment |
| Molecules implicated in transporting the peptides and loading them on the MHC molecules | TAP (transporter associated with antigen processing) | DM, invariant chain |
Read more about this topic: Major Histocompatibility Complex
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