Antigen Processing: A Beginner’s Guide
Here’s a simplified overview of MHC class I antigen processing. The ultimate product of the pathway is expression of the class I major histocompatibility complex at the surface of a cell. Cytotoxic T lymphocytes recognize the complex, and can respond by destroying abnormal cells.
Here I’ve shown a virus-infected cell, but the antigen presentation pathway goes on all the time, even in normal cells. Normal (“self”) proteins are presented on MHC class I but are ignored by CTL, because self-reactive T cells are eliminated during maturation in the thymus.
|A virus infects the cell and begins to produce …||Rarely, peptides escape this destructive process. Some of these peptides …|
|viral proteins, which (either as part of normal protein turnover or because of errors in translation) …||are translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen presentation (TAP).|
|are degraded by proteasomes in the cytosol or nucleus.||Meanwhile, new molecules of the MHC class I heavy chain …|
|Proteasomes chop the protein up into small peptides, between about 3 and 25 amino acids long.||and light chain (Î²2-microglobulin), are co-translationally translocated into the ER.|
|Any of many different peptidases (such as bleomycin hydrolase, shown here) further degrade the peptides …||As the heavy and light chain fold, with the assistance of chaperones, they assemble into a peptide-receptive complex of the MHC class I heavy chain and Î²2-microglobulin. This complex further associates with TAP and several other proteins, including tapasin.|
|all the way down to amino acids, which can be recycled into new protein synthesis.||With the help of tapasin, peptides within the ER (either with or without further trimming by ER-localized aminopeptidases) bind with the MHC class I molecule. This mature MHC class I complex, containing peptide, is allowed to leave the ER and reach the cell surface, where it can be recognized by CTL.|