BACKGROUND Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia virus, is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly prolonged course involving persistent lymphocytosis and B-cell lymphoma. The bovine major histocompatibility complex class II region plays a key role in the subclinical progression of BLV infection. In this study, we aimed to evaluate the roles of CD4+ T-cell epitopes in disease progression in cattle. METHODS We examined five Japanese Black cattle, including three disease-susceptible animals, one disease-resistant animal, and one normal animal, classified according to genotyping of bovine leukocyte antigen (BoLA)-DRB3 and BoLA-DQA1 alleles using polymerase chain reaction sequence-based typing methods. All cattle were inoculated with BLV-infected blood collected from BLV experimentally infected cattle and then subjected to CD4+ T-cell epitope mapping by cell proliferation assays. RESULTS Five Japanese Black cattle were successfully infected with BLV, and CD4+ T-cell epitope mapping was then conducted. Disease-resistant and normal cattle showed low and moderate proviral loads and harbored six or five types of CD4+ T-cell epitopes, respectively. In contrast, the one of three disease-susceptible cattle with the highest proviral load did not harbor CD4+ T-cell epitopes, and two of three other cattle with high proviral loads each had only one epitope. Thus, the CD4+ T-cell epitope repertoire was less frequent in disease-susceptible cattle than in other cattle. CONCLUSION Although only a few cattle were included in this study, our results showed that CD4+ T-cell epitopes may be associated with BoLA-DRB3-DQA1 haplotypes, which conferred differential susceptibilities to BLV proviral loads. These CD4+ T-cell epitopes could be useful for the design of anti-BLV vaccines targeting disease-susceptible Japanese Black cattle. Further studies of CD4+ T-cell epitopes in other breeds and using larger numbers of cattle with differential susceptibilities are required to confirm these findings.

中文翻译：

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五个白血病牛对牛白血病病毒CD4 + T细胞表位的定位，对牛白血病病毒疾病进展的敏感性不同。

背景技术与人T细胞白血病病毒密切相关的牛白血病病毒（BLV）是动物性牛白血病的病原体，该疾病的特征在于病程延长，涉及持续性淋巴细胞增多和B细胞淋巴瘤。牛的主要组织相容性复合物II类区域在BLV感染的亚临床进展中起关键作用。在这项研究中，我们旨在评估CD4 + T细胞表位在牛疾病进展中的作用。方法我们采用聚合酶链反应序列，根据牛白细胞抗原（BoLA）-DRB3和BoLA-DQA1等位基因的基因分型，对五只日本黑牛进行了检查，包括三只易感疾病动物，一只抗病动物和一只正常动物。基于打字的方法。所有牛都接种了从BLV实验感染的牛身上收集的BLV感染的血液，然后通过细胞增殖试验进行CD4 + T细胞表位作图。结果5只日本黑牛成功感染了BLV，然后进行了CD4 + T细胞表位作图。抗病和正常的牛表现出较低和中等的前病毒载量，分别具有六种或五种CD4 + T细胞表位。相比之下，前病毒载量最高的三只易感疾病的牛之一没有CD4 + T细胞表位，而其他前病毒载量高的三只牛中的两只都只有一个表位。因此，易感疾病的牛的CD4 + T细胞表位组成比其他牛少。结论尽管本研究只包括了几头牛，我们的结果表明，CD4 + T细胞表位可能与BoLA-DRB3-DQA1单倍型相关，这赋予了BLV前病毒载量不同的敏感性。这些CD4 + T细胞表位可用于设计针对易感疾病的日本黑牛的抗BLV疫苗。需要进一步研究其他品种的CD4 + T细胞表位，并使用大量易感性不同的牛来证实这些发现。