Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705
Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705
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DOI：
10.1002/eji.200425724
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Bowness, P
中科院分区：
文献类型：
--
作者：
Stewart-Jones, GBE;di Gleria, K;Bowness, P
我们解析了三种 HLA-B*2705 肽复合物与免疫显性病毒肽的晶体结构：EBV EBNA3C 258-266 (RRIYDLIEL)、流感 (flu) 核蛋白 NP383-391 (SRYWAIRTR) 和 HIV gag 264-273 (KRWIILGLNK)。 HIV 感染期间的长期不进展与 HLA-B*2705 的呈递以及高度免疫显性的 KRWIILGLNK 肽的 T 细胞识别有关。在 HLA-B*2705 B 袋和肽 P2 精氨酸胍锚之间观察到的紧密氢键网络解释了为什么 HIV 感染期间该残基的突变会导致肽结合丧失、免疫逃逸和进展为 AIDS。这些肽内突出的、暴露于溶剂的结构可能参与产生针对这些免疫显性表位的 T 细胞反应。在 HLA-B*2705 与流感 NP383-391 的复合物中，残基 4、7 和 8 的氨基酸侧链暴露在溶剂中，而在 HIV 十聚体中，主链在 P7 周围凸入溶剂中。因此，HLA-B*2705 呈现一系列构象的病毒肽。 HLA-B*2705 与 HIV 和流感肽（而非 EBV 肽）的四聚体复合物与杀伤性 Ig 样受体 (KIR)3DL1 强烈结合。将 EBV P8 谷氨酸替换为苏氨酸可以被 KIR3DL1 识别。在 HLA-B*2705-EBV 结构中，P8 谷氨酸侧链暴露于溶剂，可能通过静电力抑制 KIR3DL1 结合。
We have solved the crystal structures of three HLA-B*2705-peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258-266 (RRIYDLIEL), influenza (flu) nucleoprotein NP383-391 (SRYWAIRTR), and HIV gag 264-273 (KRWIILGLNK). Long-term non-progression during HIV infection has been associated with presentation by HLA-B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen-bonding network observed between the HLA-B*2705 B-pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent-exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA-B*2705 complex with flu NP383-391, the amino acid side chains of residues 4, 7 and 8 are solvent-exposed whilst in the HIV decamer, the main-chain bulges into the solvent around P7. Thus, HLA-B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA-B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer-Ig-like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA-B*2705-EBV structure the P8 glutamate side chain is solvent-exposed and may inhibit KIR3DL1 binding through electrostatic forces.