Glycosylation plays a crucial role in the folding, structure, quality control and trafficking of glycoproteins. Here, we explored whether the glycosylation status of MHC class I (MHC-I) molecules impacts their affinity for the peptide editor, TAPBPR. We demonstrate that the interaction between TAPBPR and MHC-I is stronger when MHC-I lacks a glycan. Subsequently, TAPBPR can dissociate peptides, even those of high affinity, more easily from non-glycosylated MHC-I compared to their glycosylated counterparts. In addition, TAPBPR is more resistant to peptide-mediated allosteric release from non-glycosylated MHC-I compared to species with a glycan attached. Consequently, we find the glycosylation status of HLA-A*68:02, -A*02:01 and –B*27:05 influences their ability to undergo TAPBPR-mediated peptide exchange. The discovery that the glycan attached to MHC-I significantly influences the affinity of their interactions with TAPBPR has important implications, on both an experimental level and in a biological context.

糖基化在糖蛋白的折叠、结构、质量控制和运输中起着至关重要的作用。在这里，我们探讨了 MHC I 类 (MHC-I) 分子的糖基化状态是否会影响它们对肽编辑器 TAPBPR 的亲和力。我们证明当 MHC-I 缺乏聚糖时，TAPBPR 和 MHC-I 之间的相互作用更强。随后，与糖基化对应物相比，TAPBPR 可以更容易地从非糖基化 MHC-I 中分离肽，即使是那些具有高亲和力的肽。此外，与连接有聚糖的物种相比，TAPBPR 对肽介导的非糖基化 MHC-I 的变构释放更具抵抗力。因此，我们发现 HLA-A*68:02、-A*02:01 和 –B*27:05 的糖基化状态影响它们进行 TAPBPR 介导的肽交换的能力。