Preferential interaction of MHC class I with TAPBPR in the absence of glycosylation.

Neerincx, Andreas 
Boyle, Louise H 

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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.

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Antigen processing and presentation, MHC, N-linked glycosylation, TAPBPR/TAPBPL, Tapasin, Calreticulin, Cell Line, Tumor, Endoplasmic Reticulum, Genes, MHC Class I, Glycosylation, HeLa Cells, Histocompatibility Antigens Class I, Humans, Immunoglobulins, Membrane Proteins, Membrane Transport Proteins, Peptides, Protein Disulfide-Isomerases
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Mol Immunol
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Elsevier BV
Wellcome Trust (104647/Z/14/Z)