Preferential interaction of MHC class I with TAPBPR in the absence of glycosylation.
Boyle, Louise H
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Neerincx, A., & Boyle, L. H. (2019). Preferential interaction of MHC class I with TAPBPR in the absence of glycosylation.. Mol Immunol, 113 58-66. https://doi.org/10.1016/j.molimm.2018.06.269
We recently discovered that TAPBPR promotes reglucosylation of the N-linked glycan on MHC class I molecules, a modification that restores their recognition by calreticulin and reincorporation into the peptide-loading complex. We wondered whether TAPBPR displayed some degree of glycan specificity, as is known to be the case for tapasin via its interaction with calreticulin & ERp57, or whether its interaction with MHC class I was glycan independent. Here, we explored this by comparing the ability of TAPBPR to bind to MHC class I containing either an intact or disrupted NxS/T glycosylation consensus sequence. In contrast to tapasin, TAPBPR bound strongly to MHC class I molecules that lacked N-linked glycosylation, suggesting that the TAPBPR:MHC class I interaction is glycan independent. Furthermore, we found that glycosylated HLA-A2 preferentially interacts with tapasin rather than TAPBPR, possibly explaining, in part, why MHC class I molecules bind efficiently to tapasin in the face of an alternative chaperone. The distinction in glycan specificity between the two peptide editors suggests that TAPBPR may bind to MHC class I molecules that are associated with a broader diversity of oligosaccharides attached compared with tapasin. This may explain, to some extent, the ability of TAPBPR to interact with MHC class I molecules outside of the ER.
Cell Line, Tumor, Hela Cells, Endoplasmic Reticulum, Humans, Peptides, Immunoglobulins, Calreticulin, Membrane Transport Proteins, Membrane Proteins, Histocompatibility Antigens Class I, Genes, MHC Class I, Glycosylation, Protein Disulfide-Isomerases
Wellcome Trust (104647/Z/14/Z)
External DOI: https://doi.org/10.1016/j.molimm.2018.06.269
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280032
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/