Recycling MHC Class I Molecules and Endosomal Peptide Loading

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 a...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.18.10326