Morozov Giora I, Zhao Huaying, Mage Michael G, Boyd Lisa F, Jiang Jiansheng, Dolan Michael A, Venna Ramesh, Norcross Michael A, McMurtrey Curtis P, Hildebrand William, Schuck Peter, Natarajan Kannan, Margulies David H
Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering/National Institutes of Health, Bethesda, MD 20892;
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1006-15. doi: 10.1073/pnas.1519894113. Epub 2016 Feb 11.
Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.
主要组织相容性复合体I类（MHC-I）分子的肽装载对于抗原呈递、自身耐受性和CD8(+) T细胞活化至关重要。TAP结合蛋白相关蛋白（TAPBPR）是一种广泛表达的塔帕辛同源物，不属于经典的MHC-I肽装载复合体（PLC）。利用重组MHC-I分子，我们发现TAPBPR可结合HLA-A*02:01以及其他几种无肽或装载有低亲和力肽的MHC-I分子。荧光偏振实验证实，TAPBPR可增强MHC-I的肽结合能力。TAPBPR/MHC-I相互作用可被与其亲和力相关的特定肽逆转。突变和小角X射线散射（SAXS）研究证实了TAPBPR与塔帕辛的结构相似性。这些结果支持TAPBPR在稳定MHC-I的肽接受构象、允许肽编辑方面发挥作用。
