The pathway for processing leader-derived peptides that regulate the maturation and expression of Qa-1b.
Qa-1b and its human homolog, HLA-E, predominantly bind leader peptides derived from other class I molecules. Their presentation is TAP-dependent and proteasome-independent. We demonstrate that Dd targeted to the cytosol does not generate the Qa-1b peptide epitope even in the presence of lactacystin. Cells expressing herpes virus ICP-47 block the generation of this epitope, demonstrating that TAP functions in the transport of the peptide from cytosol to ER. This reveals a pathway for antigen presentation of leader peptides that involves translocation of a protein to the ER where its leader is cleaved followed by its release into the cytosol and transport back into the ER. Further, it ensures that Qa-1b expression mirrors the normal expression of class Ia molecules.
Department of Microbiology, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
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Bai
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Broen
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Forman
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D021382:Protein Sorting Signals; C032907:Q surface antigens; C067713:lactacystin; D000111:Acetylcysteine