通过免疫信息学和表位组分析揭示了蛇毒细胞毒素的功能表位
Jia Jin Hiu1, Jared Kah Yin Fung1, Hock Siew Tan1
1School of Science, Monash University Malaysia, 47500, Bandar Sunway, Malaysia.
Scientific reports
|July 28, 2023
概括
蛇毒细胞毒素 (CTX) 造成严重的皮肤损伤,但抗毒素的向很差. 这项研究确定了关键的CTX表位序列,对于开发有效的向抗毒疗法至关重要.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 毒理学 毒理学 毒理学
背景情况:
- 细胞毒素 (CTX) 占蛇毒的70%左右,导致皮肤瘤症状.
- CTX具有较低的免疫性,使目前的抗毒疗法对其毒性无效.
- CTX的表皮特征在很大程度上仍未被描述,阻碍了实证抗毒药的开发.
研究的目的:
- 确定蛇毒细胞毒素 (CTX) 的T细胞和B细胞表皮图序列.
- 确定开发新型CTX特异性抗毒疗法的潜在目标.
主要方法:
- 使用了免疫信息学分析和表位基因组学分析.
- 用各种人类白细胞抗原 (HLA) 进行了分子对接模拟.
- 多酶有限消化/液体染色学质谱法 (MELD/LC-MS) 用于表位标识.
主要成果:
- 确定了四种潜在的CTX表位序列:"KLVPLFYK"",AGKNL"",MFMVSTPKVPV"和"DVCPKNSLL".
- HLA-B62超型对CTX具有最高的结合亲和力,特定的氨基酸残留参与相互作用.
- 局部定向突变发生证实这些表位位于CTX折叠和细胞毒性关键的功能环.
结论:
- 在功能循环中存在的已识别的CTX表位是基于合成表位的抗毒生产的潜在目标.
- 这些发现为开发更有效,更有针对性的抗毒疗法,以对抗蛇毒的方法铺平了道路.
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