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首页> 外文期刊>Clinical and vaccine immunology: CVI >Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity
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Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

机译：禽和人类季节性流感血凝素蛋白可激发抗原决定簇丰度和多样性可比的CD4 T细胞应答

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Avian influenza viruses remain a significant concern due to their pandemic potential. Vaccine trials have suggested that humans respond poorly to avian influenza vaccines relative to seasonal vaccines. It is important to understand, first, if there is a general deficiency in the ability of avian hemagglutinin (HA) proteins to generate immune responses and, if so, what underlies this defect. This question is of particular interest because it has been suggested that in humans, the poor immunogenicity of H7 vaccines may be due to a paucity of CD4 T cell epitopes. Because of the generally high levels of cross-reactive CD4 T cells in humans, it is not possible to compare the inherent immunogenicities of avian and seasonal HA proteins in an unbiased manner. Here, we empirically examine the epitope diversity and abundance of CD4 T cells elicited by seasonal and avian HA proteins. HLA-DR1 and HLA-DR4 transgenic mice were vaccinated with purified HA proteins, and CD4 T cells to specific epitopes were identified and quantified. These studies revealed that the diversity and abundance of CD4 T cells specific for HA do not segregate on the basis of whether the HA was derived from human seasonal or avian influenza viruses. Therefore, we conclude that failure in responses to avian vaccines in humans is likely due to a lack of cross-reactive CD4 T cell memory perhaps coupled with competition with or suppression of naive, HA-specific CD4 T cells by memory CD4 T cells specific for more highly conserved proteins.
机译：禽流感病毒由于具有大流行的潜力而仍然引起人们的极大关注。疫苗试验表明，相对于季节性疫苗，人类对禽流感疫苗的反应较差。首先，重要的是要了解禽血凝素（HA）蛋白质产生免疫反应的能力是否普遍存在缺陷，如果是，则该缺陷的根源是什么。这个问题特别令人感兴趣，因为已经表明在人类中，H7疫苗的免疫原性很差，可能是由于CD4 T细胞表位不足所致。由于人类中交叉反应性CD4 T细胞的水平通常很高，因此不可能以无偏见的方式比较禽类和季节性HA蛋白的固有免疫原性。在这里，我们从经验上检查季节性和禽类HA蛋白引起的CD4 T细胞的表位多样性和丰度。用纯化的HA蛋白接种HLA-DR1和HLA-DR4转基因小鼠，并对特定表位的CD4 T细胞进行鉴定和定量。这些研究表明，针对HA特异的CD4 T细胞的多样性和丰富度不会根据HA是否源自人类季节性或禽流感病毒而分离。因此，我们得出结论，人类对禽疫苗的反应失败很可能是由于缺乏交叉反应性CD4 T细胞记忆，可能是由于与之特异性结合的记忆CD4 T细胞与幼稚的HA特异性CD4 T细胞竞争或抑制。高度保守的蛋白质。

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