Department of Pathology, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3465-70. doi: 10.1073/pnas.1222342110. Epub 2013 Feb 11.
Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR:MHC class I complex trafficks through the Golgi apparatus, demonstrating a function of TAPBPR beyond the endoplasmic reticulum/cis-Golgi. The identification of TAPBPR as an additional component of the MHC class I antigen-presentation pathway demonstrates that mechanisms controlling MHC class I expression remain incompletely understood.
Tapasin 是肽加载复合物（PLC）的一个组成部分，对于 MHC I 分子有效加载肽至关重要。我们研究了 tapasin 相关蛋白 TAPBPR 的功能。与 tapasin 一样，TAPBPR 广泛表达，IFN-γ诱导，与 MHC I 结合，并与内质网中的β2-微球蛋白结合。与 tapasin 不同，TAPBPR 不与 ERp57 或钙网蛋白结合，也不是 PLC 的组成部分。β2-微球蛋白是 TAPBPR 与 MHC I 结合所必需的。然而，TAPBPR 与 MHC I 的结合发生在没有功能性 PLC 的情况下，表明不需要肽。TAPBPR 的表达通过分泌途径降低 MHC I 成熟的速度，并延长 MHC I 在 PLC 上的结合。TAPBPR:MHC I 复合物通过高尔基体运输，证明 TAPBPR 的功能超越了内质网/顺式高尔基体。将 TAPBPR 鉴定为 MHC I 抗原呈递途径的另一个组成部分表明，控制 MHC I 表达的机制仍不完全清楚。
