Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany.
Elife. 2020 Mar 13;9:e55326. doi: 10.7554/eLife.55326.
Adaptive immunity vitally depends on major histocompatibility complex class I (MHC I) molecules loaded with peptides. Selective loading of peptides onto MHC I, referred to as peptide editing, is catalyzed by tapasin and the tapasin-related TAPBPR. An important catalytic role has been ascribed to a structural feature in TAPBPR called the scoop loop, but the exact function of the scoop loop remains elusive. Here, using a reconstituted system of defined peptide-exchange components including human TAPBPR variants, we uncover a substantial contribution of the scoop loop to the stability of the MHC I-chaperone complex and to peptide editing. We reveal that the scoop loop of TAPBPR functions as an internal peptide surrogate in peptide-depleted environments stabilizing empty MHC I and impeding peptide rebinding. The scoop loop thereby acts as an additional selectivity filter in shaping the repertoire of presented peptide epitopes and the formation of a hierarchical immune response.
适应性免疫在很大程度上依赖于负载肽的主要组织相容性复合体 I 类 (MHC I) 分子。将肽选择性加载到 MHC I 上，称为肽编辑，由 tapasin 和 tapasin 相关的 TAPBPR 催化。 scoop 环的结构特征被认为在 TAPBPR 中具有重要的催化作用，但 scoop 环的确切功能仍然难以捉摸。在这里，我们使用包括人 TAPBPR 变体在内的定义明确的肽交换成分的重组系统，揭示了 scoop 环对 MHC I 伴侣复合物稳定性和肽编辑的重要贡献。我们揭示了 TAPBPR 的 scoop 环在肽耗尽环境中作为内部肽替代物发挥作用，稳定空的 MHC I 并阻碍肽重新结合。因此，scoop 环作为另一个选择性过滤器，用于塑造呈递的肽表位库和形成分层免疫反应。
