Major histocompatibility complex (MHC-I) proteins select repertoires of epitopic peptides to display on the cell surface for T cell surveillance, against a vast background of possible decoys. However, the molecular mechanism of this selection, or proofreading, process has remained unclear. Here, we capture a structural snapshot of an MHC-I molecule caught in the act of scrutinizing a potential peptide antigen under the guidance of its molecular chaperone, TAPBPR. The structure shows how conserved MHC-I residues capture the peptide backbone, to enable rapid screening of peptide decoys. TAPBPR facilitates peptide selection by stabilizing this intermediate state rather than directly competing with peptides. These findings advance our understanding of immunogenic epitope selection, with implications for vaccine development and T cell–based therapies.
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机译：主要组织相容性复合体 （MHC-I） 蛋白选择表位肽库显示在细胞表面，以便在可能的诱饵的巨大背景下进行 T 细胞监测。然而，这种选择或校对过程的分子机制仍不清楚。在这里，我们捕获了 MHC-I 分子的结构快照，该分子在其分子伴侣 TAPBPR 的指导下检查潜在肽抗原的行为中被捕获。该结构显示了保守的 MHC-I 残基如何捕获肽骨架，以实现肽诱饵的快速筛选。TAPBPR 通过稳定这种中间状态而不是直接与肽竞争来促进肽的选择。这些发现促进了我们对免疫原性表位选择的理解，对疫苗开发和基于 T 细胞的疗法具有重要意义。
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