Conformational Dimorphism of Self-peptides and Molecular Mimicry in a Disease-associated HLA-B27 Subtype*
Conformational Dimorphism of Self-peptides and Molecular Mimicry in a Disease-associated HLA-B27 Subtype*
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疾病相关 HLA-B27 亚型中自肽的构象二态性和分子拟态*
DOI：
10.1074/jbc.m508528200
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发表时间：
2006
影响因子：
4.8
通讯作者：
B. Uchánska‐Ziegler
中科院分区：
文献类型：
--
作者：
Christine Rückert;M. Fiorillo;B. Loll;R. Moretti;J. Biesiadka;W. Saenger;A. Ziegler;R. Sorrentino;B. Uchánska‐Ziegler
由主要组织相容性复合体（MHC）分子呈递的某些肽的一个有趣的性质是它们在肽结合沟内获得双重结合模式。使用1.4A分辨率的X射线晶体学，我们在此显示胰高血糖素受体衍生的自身肽pGR（412 RRWHRWRL 420）也由疾病相关的人MHC I类亚型HLA-B*2705以双重构象呈递，在两种结合模式中，肽的中间朝向分子的肽结合沟的底部弯曲。这里将pGR的构象与另一种自身肽（pVIPR，RRKWRRWHL）的构象进行比较，所述自身肽也以两种结合模式被HLA-B*2705抗原展示，并且与病毒肽pLMP 2（RRRWRRLTV）的构象进行比较。保守的结构特征表明，N-末端的一半的肽是至关重要的，在允许细胞毒性T淋巴细胞（CTL）的交叉反应。此外，对来自pGR或pVIPR定向的HLA-B27限制性CTL克隆的T细胞受体（TCR）的分析表明，来自不同克隆但具有相当反应性的TCR可能共享CDR 3 α区，但不共享CDR 3 β区。因此，这些CTL的交叉反应性取决于TCR-CDR 3 α，受TCR-CDR 3 β序列调节，并且最终是表征自身肽与HLA-B*2705结合的构象二型性的结果。这些结果支持了MHC I类结合肽的构象二型性可能与自身反应性CTL的发生有关的概念。
An interesting property of certain peptides presented by major histocompatibility complex (MHC) molecules is their acquisition of a dual binding mode within the peptide binding groove. Using x-ray crystallography at 1.4 Å resolution, we show here that the glucagon receptor-derived self-peptide pGR (412RRRWHRWRL420) is presented by the disease-associated human MHC class I subtype HLA-B*2705 in a dual conformation as well, with the middle of the peptide bent toward the floor of the peptide binding groove of the molecule in both binding modes. The conformations of pGR are compared here with those of another self-peptide (pVIPR, RRKWRRWHL) that is also displayed in two binding modes by HLA-B*2705 antigens and with that of the viral peptide pLMP2 (RRRWRRLTV). Conserved structural features suggest that the N-terminal halves of the peptides are crucial in allowing cytotoxic T lymphocyte (CTL) cross-reactivity. In addition, an analysis of T cell receptors (TCRs) from pGR- or pVIPR-directed, HLA-B27-restricted CTL clones demonstrates that TCR from distinct clones but with comparable reactivity may share CDR3α but not CDR3β regions. Therefore, the cross-reactivity of these CTLs depends on TCR-CDR3α, is modulated by TCR-CDR3β sequences, and is ultimately a consequence of the conformational dimorphism that characterizes binding of the self-peptides to HLA-B*2705. These results lend support to the concept that conformational dimorphisms of MHC class I-bound peptides might be connected with the occurrence of self-reactive CTL.
影响因子：
5.2
作者：
Khan, MA;Ball, EJ
通讯作者：
Ball, EJ
DOI：
10.1073/pnas.89.8.3429
发表时间：
1992-04-15
影响因子：
11.1
作者：
GARBOCZI, DN;HUNG, DT;WILEY, DC
通讯作者：
WILEY, DC
影响因子：
2.9
作者：
Sanner, MF;Olson, AJ;Spehner, JC
通讯作者：
Spehner, JC