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. Author manuscript; available in PMC: 2013 Jun 8.
Published in final edited form as: Cold Spring Harb Perspect Med. 2012 Aug 1;2(8):10.1101/cshperspect.a007658 a007658. doi: 10.1101/cshperspect.a007658

Figure 3.

Figure 3

Hypothesis: ERAD of misfolded secretory pathway proteins triggers MHC class I loading and presentation of autoantigens. In the case of misfolded secretory pathway proteins, retrotrans location from the ER to the cytosol triggers degradation via the ubiquitin-proteasome system. The generation of small cleavage fragments and their transport back into the ER lumen allows for peptide loading of MHC class I (via the TAP/tapasin complex). Cell stress can promote ER misfolding of secretory and membrane proteins (Kuznetsov and Nigam 1998) and also may promote expression of major histocompatibility complex class I-related genes (Groh et al. 1996). Thus, it is a plausible hypothesis that the net result of these two effects is enhanced β-cell autoantigen presentation.