Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

• The melanoma antigen tyrosinase binds to the chaperone BAG6.
• BAG6 depletion does not affect class I presentation of the ERAD substrate tyrosinase.
• BAG6 is dispensable for normal MHC class I cell surface expression.
• BAG6 is not required for class I presentation of the DRiP substrate LCMV-NP.
• Previously proposed role for BAG6 in MHC class I presentation could not be confirmed.

Antigen processing for direct presentation on MHC class I molecules is a multistep process requiring the concerted activity of several cellular complexes. The essential steps at the beginning of this pathway, namely protein synthesis at the ribosome and degradation via the proteasome, have been known for years. Nevertheless, there is a considerable lack of factors identified to function between protein synthesis and degradation during antigen processing. Here, we analyzed the impact of the chaperone BAG6 on MHC class I cell surface expression and presentation of virus-derived peptides. Although an essential role of BAG6 in antigen processing has been proposed previously, we found BAG6 to be dispensable in this pathway. Still, interaction of BAG6 and the model antigen tyrosinase was enhanced during proteasome inhibition pointing towards a role of BAG6 in antigen degradation. Redundant chaperone pathways potentially mask the contribution of BAG6 to antigen processing and presentation.

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