Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Mol Immunol. 2021 Nov;139:168-176. doi: 10.1016/j.molimm.2021.09.007. Epub 2021 Sep 20.
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-A68:02, -A02:01 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其与肽编辑酶 TAPBPR 的亲和力。我们证明，当 MHC-I 缺乏聚糖时，TAPBPR 与 MHC-I 的相互作用更强。随后，与糖基化的 MHC-I 相比，TAPBPR 可以更容易地从非糖基化的 MHC-I 上解离肽，即使是那些具有高亲和力的肽。此外，与具有聚糖的物种相比，TAPBPR 对非糖基化的 MHC-I 上肽介导的变构释放更具抵抗力。因此，我们发现 HLA-A68:02、-A02:01 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。发现 MHC-I 上附着的聚糖显著影响它们与 TAPBPR 相互作用的亲和力，这在实验和生物学背景下都具有重要意义。
