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病毒序列决定了HLA-E受限制的T细胞对B型肝炎表面抗原的识别

Gavuthami Murugesan¹, Rachel L Paterson¹, Rakesh Kulkarni¹

¹Immunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, OX14 4RY, UK.

Nature communications

|November 23, 2024

概括

这项研究确定了一种特定的乙型肝炎病毒变体,可以通过HLA-E参与T细胞,为抗慢性乙型肝炎感染提供通用免疫治疗的潜在标.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
分子生物学分子生物学

背景情况:

慢性乙型肝炎病毒 (HBV) 感染导致T细胞功能障碍.
乙型肝炎表面抗原 (HBsAg) 有助于T细胞衰弱.
非多态的HLA-E分子是免疫疗法的潜在目标.

研究的目的:

为了表征HLA-E结合HBsAg的基因型变异 (Env371-379).
评估T细胞对由HLA-E呈现的不同HBsAg变体的功能反应.
探索HLA-E受限制的HBsAg的潜力,作为免疫治疗的标.

主要方法:

对HBsAg变体的生物信息预测.
生物化学和细胞分析以验证变异.
使用一种具有可溶性亲和度增强的T细胞受体 (TCR) -抗CD3双特异分子来探测HLA-E呈现.
与表达HBsAg.Ag的T细胞和细胞进行共同培养测定.

主要成果:

鉴定并验证了Env371-379的三个基因型变异.
只有Env371-379的L6I变体在由HLA-E呈现时引起了功能T细胞反应.
在实验室原始化后,在HBV-naive和慢性感染个体中检测到HLA-E-Env371-379 L6I特异性的CD8+ T细胞.
病毒突变会影响-HLA-E复合物的稳定性和向性.

结论:

提供了HBV Env的HLA-E介导呈现的证据.
-HLA-E复合物的稳定性对于引起T细胞反应至关重要.
特定的HBsAg变体,如L6I,是开发针对慢性HBV的通用免疫疗法的潜在目标.

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