TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E. Deane, Louise H. Boyle

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27 Citations (Scopus)
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Abstract

Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on class I, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide-editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex.

Original languageEnglish
Article numbere23049
Pages (from-to)1-25
Number of pages25
JournaleLife
Volume6
DOIs
Publication statusPublished - 20 Apr 2017

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    Neerincx, A., Hermann, C., Antrobus, R., van Hateren, A., Cao, H., Trautwein, N., Stevanović, S., Elliott, T., Deane, J. E., & Boyle, L. H. (2017). TAPBPR bridges UDP-glucose: glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway. eLife, 6, 1-25. [e23049]. https://doi.org/10.7554/eLife.23049