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.

Key
	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 (β2-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 β2-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.