Structural basis for a major histocompatibility complex class Ib-restricted T cell response
Structural basis for a major histocompatibility complex class Ib-restricted T cell response
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DOI：
10.1038/ni1312
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发表时间：
2006-03-01
影响因子：
30.5
通讯作者：
Brooks, AG
中科院分区：
文献类型：
--
作者：
Hoare, HL;Sullivan, LC;Brooks, AG
与主要组织相容性复合体（MHC） Ia类分子介导的抗原特异性免疫相反，祖先相关的非经典MHC Ib类分子通常介导先天免疫反应。在这里，我们已经证明了MHC类Ib分子HLA-E介导MHC限制性细胞毒性T淋巴细胞对人巨细胞病毒的适应性反应的结构基础。由于受到宿主遗传的高度限制，该应答对病毒肽的第8位表现出显著的精细特异性，这是区分自我与非自我的唯一标志。尽管MHC Ia类和MHC Ib类分子在进化上存在差异，但T细胞受体-MHC Ib类复合物的结构与传统的T细胞受体-MHC Ia类复合物非常相似。这些结果强调了HLA-E进化的“模糊性”，它不仅与先天免疫受体相互作用，而且在适应性免疫过程中具有介导病毒特异性细胞毒性T淋巴细胞反应的功能能力。
In contrast to antigen-specific immunity orchestrated by major histocompatibility complex (MHC) class Ia molecules, the ancestrally related nonclassical MHC class Ib molecules generally mediate innate immune responses. Here we have demonstrated the structural basis by which the MHC class Ib molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte response to human cytomegalovirus. Highly constrained by host genetics, the response showed notable fine specificity for position 8 of the viral peptide, which is the sole discriminator of self versus nonself. Despite the evolutionary divergence of MHC class Ia and class Ib molecules, the structure of the T cell receptor-MHC class Ib complex was very similar to that of conventional T cell receptor-MHC class Ia complexes. These results emphasize the evolutionary 'ambiguity' of HLA-E, which not only interacts with innate immune receptors but also has the functional capacity to mediate virus-specific cytotoxic T lymphocyte responses during adaptive immunity.