在AAV体蛋白质的HLA类I免疫体中
Carlos A Brito-Sierra1, Megan B Lannan1, Laurent P Malherbe1
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United States.
Frontiers in immunology
|September 4, 2023
概括
这项研究从腺相关病毒 (AAV) 体中识别出自然存在的HLA类I,揭示了基因治疗的新型表位体,并突出了在血清型中保存的,以潜在的交叉反应. 这有助于我们更好地理解对AAV载体的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 基因治疗 基因治疗
背景情况:
- 细胞对腺相关病毒 (AAV) 囊的免疫反应阻碍了基因治疗的成功.
- 以前的方法使用宽扫描识别了T细胞表位,但自然呈现的是未知的.
研究的目的:
- 为了识别自然显示的AAV2,AAV6和AAV9的HLA类I免疫体.
- 描述AAV特异性CD8+ T细胞上由HLA类I分子呈现的类的谱.
主要方法:
- 使用mRNA转移的单细胞衍生物树突细胞 (MDDC) 和MHC相关蛋白质组 (MAPP).
- 通过质谱学从免疫沉的:HLA复合物中化出来的分析.
主要成果:
- 确定了65个在HLAI类分子上呈现的AAV囊衍生.
- 发现这些的91%是以前未知的T细胞表位.
- 在AAV血清型中发现了11个保存,这表明潜在的交叉反应性CD8+T细胞反应.
结论:
- 这是从AAV囊中自然呈现的HLA类I的第一个综合性研究.
- 结果为评估AAV基因疗法的免疫性风险和交叉反应性提供了基础.
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