Substrate-specific presentation of MHC class I-restricted antigens via autophagy pathway
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35247713
DOI
10.1016/j.cellimm.2022.104484
PII: S0008-8749(22)00008-9
Knihovny.cz E-resources
- Keywords
- Autophagy, EBV-encoded EBNA1, MHC class I restricted antigen presentation, Protein aggregates,
- MeSH
- Antigens MeSH
- Autophagy MeSH
- Immune Evasion MeSH
- Histocompatibility Antigens Class I * MeSH
- Histocompatibility Antigens Class II metabolism MeSH
- Ovalbumin MeSH
- Antigen Presentation * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens MeSH
- Histocompatibility Antigens Class I * MeSH
- Histocompatibility Antigens Class II MeSH
- Ovalbumin MeSH
The accumulation of protein aggregates is toxic and linked to different diseases such as neurodegenerative disorders, but the role of the immune system to target and destroy aggregate-carrying cells is still relatively unknown. Here we show a substrate-specific presentation of antigenic peptides to the direct MHC class I pathway via autophagy. We observed no difference in presentation of peptides derived from the viral EBNA1 protein following suppression of autophagy by knocking down Atg5 and Atg12. However, the same knock down treatment suppressed the presentation from ovalbumin. Fusing the aggregate-prone poly-glutamine (PolyQ) to the ovalbumin had no effect on antigen presentation via autophagy. Interestingly, fusing the EBNA1-derived gly-ala repeat (GAr) sequence to ovalbumin rendered the presentation Atg5/12 independent. We also demonstrate that the relative levels of protein expression did not affect autophagy-mediated antigen presentation. These data suggest a substrate-dependent presentation of antigenic peptides for the MHC class I pathway via autophagy and indicate that the GAr of the EBNA1 illustrates a novel virus-mediated mechanism for immune evasion of autophagy-dependent antigen presentation.
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