TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst
TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst
复制标题
DOI：
10.7554/elife.09617
复制
发表时间：
2015-10-06
期刊：
影响因子：
7.7
通讯作者：
Boyle, Louise H.
中科院分区：
文献类型：
--
作者：
Hermann, Clemens;van Hateren, Andy;Boyle, Louise H.
最近，随着Tapasin相关蛋白TAPBPR是第二个主要组织相容性复合体(MHC)I类特异性伴侣的鉴定，我们对抗原提呈途径的理解得到了加强。我们试图确定，TAPBPR是否也可以像TAPASIN一样，通过起到肽交换催化剂的作用来影响MHC I类肽的选择。我们发现，TAPBPR可以催化多肽从多肽-MHC I复合体中解离，增加多肽受体MHC I分子的负载量，并在体外根据亲和力区分多肽。在细胞中，TAPBPR的缺失增加了MHC I分子上呈现的多肽的多样性，表明TAPBPR参与了限制多肽呈现的过程。我们的结果表明，TAPBPR以一种多肽接受的状态与MHC I结合，并像Tapasin一样，促进多肽优化。现在很清楚，有两个MHC I类特异性多肽编辑程序，Tapasin和TAPBPR，密切参与控制多肽向免疫系统的递送。
Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.