Recycling MHC class I molecules and endosomal peptide loading

MHC class I molecules usually present peptides derived from endogenous anti gens that are bound in the endoplasmic reticulum, Loading of exogenous anti gens on class I molecules, e.g., in cross-priming, sometimes occurs, but th e intracellular location where interaction between the antigenic fragment a nd class I takes place is unclear. Here we show that measles virus F protei n can be presented by class I in transporters associated with antigen proce ssing-independent, NH4Cl-sensitive manner, suggesting that class I molecule s are able to interact and bind antigen in acidic compartments, like class II molecules. Studies on intracellular transport of green fluorescent prote in-tagged class I molecules in living cells confirmed that a small fraction of class I molecules indeed enters classical MNC: class II compartments (M IICs) and is transported in MIICs back to the plasma membrane. Fractionatio n studies show that class I complexes in MIICs contain peptides. The pH in MIIC (around 5.0) is such that efficient peptide exchange can occur. We thu s present evidence for a pathway fur class I loading that is shared with cl ass II molecules.