Substrate-specific presentation of MHC class I-restricted antigens via autophagy pathway

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.

Automated summary

The accumulation of protein aggregates is toxic and its relation to diseases is still unclear. This study reveals that certain antigenic peptides can be presented to the MHC class I pathway via autophagy. The presentation of peptides derived from the viral EBNA1 protein was not affected by autophagy suppression, while the presentation of ovalbumin was suppressed. The study also suggests that the relative levels of protein expression do not affect autophagy-mediated antigen presentation.