Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent
Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent
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DOI：
10.1099/vir.0.18678-0
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发表时间：
2003-01-01
影响因子：
3.8
通讯作者：
Sällberg, M
中科院分区：
文献类型：
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作者：
Lazdina, U;Alheim, M;Sällberg, M
B型肝炎病毒（HBV）核心抗原（HBcAg）具有独特的结合高频率的初始人和鼠B细胞的能力。HBcAg结合幼稚B细胞在HBcAg免疫原性中的作用尚不清楚。使用具有突变的刺突区（残基76-85）序列的HBcAg颗粒表征幼稚B细胞的HBcAg结合特性。缺失残基76-85（HBcDelta 76 -85）破坏幼稚B细胞结合，而缺失残基79-85则不会。在80位具有Ile而不是天然Ala的HBcAg颗粒不结合幼稚B细胞，而Ile（80）->Ala的逆转恢复了B细胞结合。破坏HBcAg的B细胞结合能力对不同颗粒的总体B细胞免疫原性具有边际效应，这表明它们在引发T辅助细胞方面同样有效。因此，研究了HBcAg结合B细胞与HBcAg特异性细胞毒性T细胞（CTL）引发的关系。通过用内源性HBcAg（DNA免疫）和外源性重组HBcAg颗粒免疫评价HBcAg结合B细胞在HBcAg特异性CTL的引发中的作用。内源性HBcAg在野生型和B细胞缺陷小鼠中引发HBcAg特异性CTL，而外源性HBcAg仅在野生型小鼠中引发HBcAg特异性CTL。重要的是，尽管存在B细胞，HBcDelta 76 -85不引发CTL。因此，外源性HBcAg颗粒引发特异性CTL的能力是B细胞依赖性的，这表明HBcAg结合B细胞在HBV感染中的可能作用。
The hepatitis B virus (HBV) core antigen (HBcAg) has a unique ability to bind a high frequency of naive human and murine B cells. The role of HBcAg-binding naive B cells in the immunogenicity of HBcAg is not clear. The HBcAg-binding properties of naive B cells were characterized using HBcAg particles with mutated spike region (residues 76-85) sequences. Deletion of residues 76-85 (HBcDelta76-85) destroyed naive B cell binding, whereas deletion of residues 79-85 did not. HBcAg particles with an lie instead of the natural Ala at position 80 did not bind naive B cells, whereas reversion of Ile(80)-->Ala restored B cell binding. Destroying the B cell-binding ability of HBcAg had a marginal effect on the overall B cell immunogenicity of the different particles, suggesting that they were equally efficient in priming T helper cells. Therefore, the importance of HBcAg-binding B cells is studied with relation to the priming of HBcAg-specific cytotoxic T cells (CTLs). The role of HBcAg-binding B cells in the priming of HBcAg-specific CTLs was evaluated by immunization with endogenous HBcAg (DNA immunization) and exogenous recombinant HBcAg particles, Endogenous HBcAg primed HBcAg-specific CTLs in wild-type and B cell-deficient mice, whereas exogenous HBcAg primed HBcAg-specific CTLs only in wild-type mice. Importantly, HBcDelta76-85 did not prime CTLs despite the presence of B cells. Thus, the ability of exogenous HBcAg particles to prime specific CTLs is B cell dependent, suggesting a possible role for HBcAg-binding B cells in HBV infections.