Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.
Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.
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Goodpasture 自身抗原上线性 B 细胞表位关键残基的鉴定
DOI：
10.1371/journal.pone.0123277
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhao MH
中科院分区：
文献类型：
--
作者：
Jia XY;Cui Z;Li JN;Hu SY;Zhao MH
抗肾小球基底膜（GBM）疾病的自身抗原已被鉴定为IV型胶原α3链的非胶原结构域1，α3（IV）NC 1。我们先前的研究揭示了α3（IV）NC 1上的一个肽作为B细胞的主要线性表位并具有潜在的肾原性，命名为P14（α3129-150）。该肽也已被证明是抗GBM患者中自身反应性T细胞的表位。本研究旨在进一步表征P14的关键基序。入选16例抗GBM疾病和抗P14抗体阳性患者。合成了一组截短和丙氨酸取代的P14衍生肽。通过酶联免疫吸附试验（ELISA）检测针对肽的循环抗体。我们发现所有抗P14抗体的血清只与P14 C端的13-mer序列（P14 c）反应。抗P14抗体水平与抗P14 c抗体水平高度相关（r=0.970，P<0.001）。P14 c是免疫原性的核心区域，其氨基酸序列（ISLWKGFSFIMFT）是高度疏水的。P14 c中的每个氨基酸残基依次被丙氨酸取代。基于每个残基替换后抗体反应的显著下降（P<0.001），确定了甘氨酸142、苯丙氨酸143和苯丙氨酸145这三个残基对抗体结合至关重要。我们将GFxF（α3142，143，145）定义为P14的关键基序。这可能为了解抗GBM病的病因提供一些线索。
The autoantigen of anti-glomerular basement membrane (GBM) disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IV)NC1. Our previous study revealed a peptide on α3(IV)NC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150). This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14. 16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA). We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c) exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P<0.001). P14c was the core immunogenic region and the amino acid sequence (ISLWKGFSFIMFT) was highly hydrophobic. Each amino acid residue in P14c was sequentially replaced by alanine. Three residues of glycine142, phenylalanine143, and phenylalanine145 were identified crucial for antibody binding based on the remarkable decline (P<0.001) of antibody reaction after each residue replacement. We defined GFxF (α3142, 143,145) as the critical motif of P14. It may provide some clues for understanding the etiology of anti-GBM disease.
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影响因子：
15.9
作者：
BOLTON, WK;TUCKER, FL;STURGILL, BC
通讯作者：
STURGILL, BC
影响因子：
19.6
作者：
Robertson, J;Wu, J;Lou, YH
通讯作者：
Lou, YH
抗肾小球基底膜抗体表位扩散与肾损伤的关联。
DOI：
10.2215/cjn.05140512
发表时间：
2013-01-01
影响因子：
9.8
作者：
Chen, Jun-liang;Hu, Shui-yi;Zhao, Ming-hui
通讯作者：
Zhao, Ming-hui
影响因子：
5.4
作者：
STOCKINGER, B
通讯作者：
STOCKINGER, B
B细胞从T细胞中寻求自己的帮助。
DOI：
10.1084/jem.183.3.891
发表时间：
1996-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Stockinger B;Zal T;Zal A;Gray D
通讯作者：
Gray D