MHC分子构象（图）
新的研究显示MHC分子可以影响人体对接种疫苗的反应强度，这为抑制许多疫苗引起的神经炎症反应提供了可能。
该研究发表在最新一期的《Journal of Immunology》杂志上。自从2000年以来，部分关于老年痴呆症的研究一直锁定于一种β-淀粉肽类疫苗，其在脑部的积累可以引起疾病的发生。含有β-淀粉肽的疫苗可以在6%的患者中引起严重的神经炎症反应。为了开发更加安全和有效的治疗手段，研究人体对β-淀粉肽疫苗的反应机理是科学家们的必要工作。
来自INSERUM和UPMC研究小组的Pierre Aucouturier，Cécile Toly-Ndour和Guillaume Dorothée开展了关于小鼠不同类型MHC分子的研究。由于该分子主要功能是将抗原递呈给免疫细胞，并具有高度基因多样性，因此可以用来解释不同强度的免疫反应。在本研究中，使用相同的β-淀粉肽类疫苗接种小鼠，发现不同MHC类型小鼠产生了不同强度的免疫反应。然后，科学家们通过将一种小鼠的MHC传递给另一种，发现独立于遗传背景，依赖于MHC分子的，对抗β-淀粉肽有着重要作用的另一因素。最后，科学家们证实了这些因素和白细胞的一类亚群——调节性T细胞相关。
这些结果为控制细胞免疫反应开创了新思路，比如增强人体免疫力，这是目前人类抵抗老年痴呆症最有潜力的方法。研究者们表示下一步他们将开展部分人体试验。（生物探索 Jun）
相关英文论文摘要：
MHC-Independent Genetic Factors Control the Magnitude of CD4+ T Cell Responses to Amyloid-β Peptide in Mice through Regulatory T Cell-Mediated Inhibition
Accumulation of amyloid-β peptide (Aβ) is considered the triggering factor of pathogenic lesions in Alzheimer’s disease (AD), and vaccines targeting Aβ are promising therapeutic options. However, the occurrence of meningoencephalitides attributed to T cell responses in 6% of Aβ-immunized patients underscores the need for a better understanding of T cell responses to Aβ. We characterized the parameters controlling the magnitude of Aβ-specific CD4+ T cell responses in mice. T cell responsiveness to Aβ1-42 was highly heterogeneous between mouse strains of different H-2 haplotypes, with SJL/J (H-2s) mice displaying a strong response, mainly specific for Aβ10-24, and C57BL/6 (H-2b) mice displaying a weak response to Aβ16-30. Surprisingly, C57BL/6 mice congenic for the H-2s haplotype (B6.H-2S), which display a “permissive” MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4+ T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4+ T cell responses in C57BL/6 background. Vaccine-induced CD4+ T cell responses to Aβ were significantly enhanced in both C57BL/6 and B6.H-2S mice upon depletion of regulatory T cells (Tregs), whereas Treg-depleted SJL/J mice displayed unaltered Aβ-specific T cell responses. Finally, Treg depletion in C57BL/6 transgenic APPPS1 mice, a mouse model of AD, results in enhanced vaccine-induced CD4+ T cell responses in AD compared with wild-type animals. We concluded that the magnitude of Aβ-specific CD4+ T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses.
英文原文链接：https://www.jimmunol.org/content/early/2011/09/25/jimmunol.1003953.short?rss=1
