Processing of a class I-restricted epitope from tyrosinase requires peptide N-glycanase and the cooperative action of endoplasmic reticulum aminopeptidase 1 and cytosolic proteases
| Autor: | Joy M. Polefrone, Marina Ostankovitch, Michelle L. Altrich-VanLith, Victor H. Engelhard, Claudio A. Mosse, Donald F. Hunt, Jeffrey Shabanowitz |
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| Rok vydání: | 2006 |
| Předmět: |
Glycosylation
Tyrosinase Proteolysis Immunology Biology Endoplasmic Reticulum Aminopeptidase Aminopeptidases Epitope Minor Histocompatibility Antigens chemistry.chemical_compound Epitopes Cytosol HLA-A2 Antigen medicine Immunology and Allergy Humans Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Deamidation Antigen Presentation medicine.diagnostic_test HLA-A Antigens Monophenol Monooxygenase Endoplasmic reticulum Histocompatibility Antigens Class I Biochemistry chemistry Peptide Hydrolases |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(8) |
| ISSN: | 0022-1767 |
| Popis: | Although multiple components of the class I MHC processing pathway have been elucidated, the participation of nonproteasomal cytosolic enzymes has been largely unexplored. In this study, we provide evidence for multiple cytosolic mechanisms in the generation of an HLA-A*0201-associated epitope from tyrosinase. This epitope is presented in two isoforms containing either Asn or Asp, depending on the structure of the tyrosinase precursor. We show that deamidation of Asn to Asp is dependent on glycosylation in the endoplasmic reticulum (ER), and subsequent deglycosylation by peptide-N-glycanase in the cytosol. Epitope precursors with N-terminal extensions undergo a similar process. This is linked to an inability of ER aminopeptidase 1 to efficiently remove N-terminal residues, necessitating processing by nonproteasomal peptidases in the cytosol. Our work demonstrates that processing of this tyrosinase epitope involves recycling between the ER and cytosol, and an obligatory interplay between enzymes involved in proteolysis and glycosylation/deglycosylation located in both compartments. |
| Databáze: | OpenAIRE |
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