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 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, NH(4)Cl-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.
Grommé
M
M
Department of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Uytdehaag
F G
FG
Janssen
H
H
Calafat
J
J
van Binnendijk
R S
RS
Kenter
M J
MJ
Tulp
A
A
Verwoerd
D
D
Neefjes
J
J
D001402:B-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D011992:Endosomes / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006681:HLA-D Antigens / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D008459:Measles virus / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000378:metabolism
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins; D049452:Green Fluorescent Proteins