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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Loss in CD4 T-cell responses to multiple epitopes in influenza due to expression of one additional MHC class II molecule in the host
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Loss in CD4 T-cell responses to multiple epitopes in influenza due to expression of one additional MHC class II molecule in the host

机译：由于宿主中另外一种MHC II类分子的表达，使CD4 T细胞对流感中多个表位的反应丧失

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摘要

An understanding of factors controlling CD4 T-cell immunodominance is needed to pursue CD4 T-cell epitope-driven vaccine design, yet our understanding of this in humans is limited by the complexity of potential MHC class II molecule expression. In the studies described here, we took advantage of genetically restricted, well-defined mouse strains to better understand the effect of increasing MHC class II molecule diversity on the CD4 T-cell repertoire and the resulting anti-influenza immunodominance hierarchy. Interferon-γ ELISPOT assays were implemented to directly quantify CD4 T-cell responses to I-A b and I-A s restricted peptide epitopes following primary influenza virus infection in parental and F 1 hybrid strains. We found striking and asymmetric declines in the magnitude of many peptide-specific responses in F 1 animals. These declines could not be accounted for by the lower surface density of MHC class II on the cell or by antigen-presenting cells failing to stimulate T cells with lower avidity T-cell receptors. Given the large diversity of MHC class II expressed in humans, these findings have important implications for the rational design of peptide-based vaccines that are based on the premise that CD4 T-cell epitope specificity can be predicted by a simple cataloguing of an individual's MHC class II genotype.
机译：进行CD4 T细胞表位驱动的疫苗设计需要了解控制CD4 T细胞免疫优势的因素，但我们对人类的了解受到潜在MHC II类分子表达的复杂性的限制。在这里描述的研究中，我们利用了遗传受限，定义明确的小鼠品系，以更好地了解增加MHC II类分子多样性对CD4 T细胞库和由此产生的抗流感免疫优势体系的影响。实施干扰素-γELISPOT分析以直接量化亲本和F 1杂种菌株感染原发流感病毒后CD4 T细胞对I-A b和I-A s限制性肽表位的反应。我们发现F 1动物中许多肽特异性反应的幅度显着且不对称下降。这些下降的原因不能归因于细胞中II类MHC的较低表面密度，也不能归因于抗原递呈细胞未能用较低的亲和力T细胞受体刺激T细胞。鉴于人类表达的II类MHC种类繁多，这些发现对基于肽的疫苗的合理设计具有重要意义，其前提是可以通过简单分类个人的MHC来预测CD4 T细胞表位特异性II类基因型。

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