Antigen processing

From Wikipedia, the free encyclopedia

Two methods exist for an antigen to be processed and presented on the cell surface. Both MHC class I and II require a peptide to be bound for them to be stable. Otherwise, they are not expressed on the cell surface.

1 The Endogenous Pathway
2 The Exogenous Pathway
3 See also
4 References

[edit] The Endogenous Pathway

The endogenous pathway is used to present cellular peptide fragments on the cell surface on MHC class I molecules. If a virus had infected the cell, viral peptides would also be presented, allowing the immune system to recognize and kill the infected cell. Worn out proteins within the cell become ubiquitinated, marking them for proteasome degradation. Proteasomes break the protein up into peptides that include some around nine amino acids long (suitable for fitting within the peptide binding cleft of MHC class I molecules). TAP, a protein that spans the membrane of the rough endoplasmic reticulum, transports the peptides into the lumen of the rough endoplasmic reticulum (ER). Also within the rough ER, a series of chaperone proteins, including calnexin, calreticulin, ERp57, and immunoglobulin binding protein (BiP) facilitates the proper folding of class I MHC and its association with β2 microglobulin. The partially folded MHC class I molecule then interacts with TAP via tapasin (the complete complex also contains calreticulin and Erp57 and, in mice, calnexin). Once the peptide is transported into the ER lumen it binds to the cleft of the awaiting MHC class I molecule, stabilizing the MHC and allowing it to be transported to the cell surface by the golgi apparatus.

[edit] The Exogenous Pathway

The exogenous pathway is utilized by professional antigen presenting cells to present peptides derived from proteins that the cell has endocytosed. The peptides are presented on MHC class II molecules. Proteins are endocytosed and degraded by acid-dependent proteases in endosomes. The nascent MHC class II protein in the rough ER has its peptide binding cleft blocked by Ii (the invariant chain; a trimer) to prevent it from binding peptides cellular peptides or those from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then broken down in stages, leaving only a small fragment called CLIP which still blocks the peptide binding cleft. An MHC class II-like structure, HLA-DM, removes CLIP and replaces it with a peptide from the endosome. The stable MHC class-II is then presented on the cell surface.

There is also a mechanism to associate peptides from endocytosed proteins with MHC class I, termed cross-presentation.