Recycling MHC Class I Molecules and Endosomal Peptide Loading

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-08, Vol.96 (18), p.10326-10331
• Main Authors: Gromme, Monique, Fons G. C. M. Uytdehaag, Janssen, Hans, Calafat, Jero, Van Binnendijk, Robert S., Marcel J. H. Kenter, Tulp, Abraham, Verwoerd, Desiree, Neefjes, Jacques
• Format: Article
• Language: English
• Subjects: Antibodies; Antigen presenting cells; Antigens; B-Lymphocytes - immunology; Biological Sciences; Cell Line, Transformed; Cell lines; Cell Membrane - physiology; Cell membranes; Cultured cells; Endoplasmic Reticulum - physiology; endosomes; Endosomes - physiology; F protein; Green Fluorescent Proteins; Herpesvirus 4, Human - genetics; Histocompatibility Antigens Class I - physiology; HLA-D Antigens - physiology; Humans; Hydrogen-Ion Concentration; Ice; Kinetics; Luminescent Proteins - metabolism; measles virus; Measles virus - immunology; Molecules; Recombinant Fusion Proteins - metabolism; T lymphocytes; Viral Fusion Proteins - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.18.10326

MHC class I molecules usually present peptides derived from endogenous antigens that are bound in the endoplasmic reticulum. Loading of exogenous antigens on class I molecules, e.g., in cross-priming, sometimes occurs, but the intracellular location where interaction between the antigenic fragment and class I takes place is unclear. Here we show that measles virus F protein can be presented by class I in transporters associated with antigen processing-independent, NH4Cl- sensitive manner, suggesting that class I molecules are able to interact and bind antigen in acidic compartments, like class II molecules. Studies on intracellular transport of green fluorescent protein-tagged class I molecules in living cells confirmed that a small fraction of class I molecules indeed enters classical MHC class II compartments (MIICs) and is transported in MIICs back to the plasma membrane. Fractionation 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 thus present evidence for a pathway for class I loading that is shared with class II molecules.