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A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins.
A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Jun 15; Vol. 178 (12), pp. 7932-42. - Publication Year :
- 2007
-
Abstract
- MHC class I molecules present peptides derived from the ectodomains of endogenous transmembrane proteins; however, the processing of these Ags is incompletely understood. As model transmembrane Ags we investigated the processing of MHC-I-derived fusion proteins containing the N-terminally extended K(b)-restricted OVA epitope SIINFEKL in the extracytoplasmic domain. In TAP-deficient, nonprofessional APCs, the epitope was cleaved out of various sequence contexts and presented to T cells. Ag presentation was inhibited by acidophilic amines and inhibitors of the vacuolar proton pump, indicating processing in endosomes. Endosomal aspartic-type cathepsins, and to some extent also the trans-Golgi network protease furin, were involved in processing. Clathrin-dependent and independent internalization from the cell surface targeted MHC-I fusion proteins to early and late endosomes, where SIINFEKL/K(b) complexes were detected by immunofluorescence microscopy. Targeting of MHC-I fusion proteins to processing compartments was independent of sequence motifs in the cytoplasmic tail. Not only TAP-deficient cells, but also TAP-competent APCs used the vacuolar pathway for processing of MHC-I fusion proteins. Thus, endosomal processing of internalized endogenous transmembrane proteins represents a novel alternate pathway for the generation of MHC-I-binding peptides.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters genetics
Amino Acid Sequence
Aminopeptidases metabolism
Animals
Aspartic Acid chemistry
Cathepsins metabolism
Cell Membrane metabolism
Egg Proteins metabolism
Endosomes immunology
Furin metabolism
Histocompatibility Antigens Class I immunology
Hydrogen-Ion Concentration
Mice
Mice, Mutant Strains
Minor Histocompatibility Antigens
Molecular Sequence Data
Ovalbumin metabolism
Peptide Fragments
Peptides immunology
Peptides metabolism
Recombinant Fusion Proteins metabolism
Vacuoles metabolism
ATP-Binding Cassette Transporters metabolism
Antigen Presentation
Endosomes enzymology
Histocompatibility Antigens Class I metabolism
Membrane Proteins immunology
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17548631
- Full Text :
- https://doi.org/10.4049/jimmunol.178.12.7932