Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg.
Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg.
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DOI：
10.4049/jimmunol.139.4.1223
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发表时间：
1987-08
影响因子：
4.4
通讯作者：
D. Milich;Alan McLachlan;A M Moriarty;G. B. Thornton
中科院分区：
文献类型：
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作者：
D. Milich;Alan McLachlan;A M Moriarty;G. B. Thornton
B型肝炎病毒核衣壳颗粒（HBcAg）可作为T细胞非依赖性抗原注射到无胸腺小鼠体内。然而，用HBcAg免疫正常胸腺小鼠导致抗HBc滴度显著增加。因此，我们研究了小鼠T细胞对HBcAg的免疫原性，H-2连接基因的影响，以及使用合成肽类似物识别T细胞的良好特异性。HBcAg被证明是一种非常有效的免疫原，在T细胞活化方面，通过诱导T细胞致敏所需的体内剂量（1.0微克）和诱导白细胞介素2（IL 2）产生所需的最小体外浓度（0.03 ng/ml）来测量。HBcAg的T细胞免疫原性程度及其直接激活B细胞的能力最有可能解释正常胸腺小鼠和HBV感染患者对HBcAg的体液应答增强。H-2连锁基因对HBcAg体液应答的影响是可辨别的，并鉴定了高应答（H-2k，s，d），中等应答（H-2b，f）和低应答（H-2 p）单倍型。H-2连接的调节T细胞反应与体内抗HBc的产生相关。对T细胞识别的精细特异性的检查显示，来自各种菌株的HBcAg特异性T细胞识别HBcAg/HBeAg序列内的多个但不同的位点。T细胞识别位点由小（16至21个残基）合成肽限定。每个菌株识别一个占主导地位的T细胞决定簇，这种识别过程的精细特异性取决于响应菌株的H-2单倍型。如H-2s、B株主要识别p120-140，H-2f、q株主要识别p100-120，H-2d株主要识别p85-100。因为这些序列是HBcAg和非颗粒形式的抗原HBeAg共同的，所以这些结果表明HBcAg和HBeAg在T细胞水平上是高度交叉反应的，尽管它们在血清学上是不同的。这些发现可能具有临床意义，因为T细胞对HBeAg的敏感性和随后的抗-HBe状态的血清转换与B型肝炎感染期间的病毒清除相关。
Hepatitis B virus nucleocapsid particles (HBcAg) can function as a T cell-independent antigen when injected into athymic mice. However, immunization of euthymic mice with HBcAg results in dramatically increased anti-HBc titers. Therefore we have examined the murine T cell response to HBcAg in terms of immunogenicity, the influence of H-2-linked genes, and the fine specificity of T cell recognition using synthetic peptide analogs. The HBcAg was shown to be an extremely efficient immunogen in terms of T cell activation as measured by the in vivo dose required to induce T cell sensitization (1.0 microgram), and the minimal in vitro concentration required to elicit interleukin 2 (IL 2) production (0.03 ng/ml). The degree of T cell immunogenicity of HBcAg and its ability to directly activate B cells most likely explain the enhanced humoral response to HBcAg in euthymic mice and HBV-infected patients. The influence of H-2-linked genes on the humoral response to HBcAg was discernable, and high responder (H-2k,s,d), intermediate responder (H-2b,f), and low responder (H-2p) haplotypes were identified. The H-2-linked regulation of the T cell response correlated with in vivo anti-HBc production. Examination of the fine specificity of T cell recognition revealed HBcAg-specific T cells from a variety of strains recognize multiple but distinct sites within the HBcAg/HBeAg sequence. T cell recognition sites were defined by small (16 to 21 residue) synthetic peptides. Each strain recognized a predominant T cell determinant, and the fine specificity of this recognition process was dependent on the H-2 haplotype of the responding strain. For example H-2s,b strains recognized p120-140, H-2f,q strains recognized p100-120, and H-2d mice recognized p85-100 predominantly. Because these sequences are common to both HBcAg and a nonparticulate form of the antigen termed HBeAg, these results indicate that HBcAg and HBeAg are highly cross-reactive at the T cell level although they are serologically distinct. These findings may have clinical relevance, because T cell sensitization to HBeAg and the subsequent seroconversion to anti-HBe status correlates with viral clearance during hepatitis B infection.