Monsonego Alon, Zota Victor, Karni Arnon, Krieger Jeffery I, Bar-Or Amit, Bitan Gal, Budson Andrew E, Sperling Reisa, Selkoe Dennis J, Weiner Howard L
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Clin Invest. 2003 Aug;112(3):415-22. doi: 10.1172/JCI18104.
Alzheimer disease (AD) is characterized by the progressive deposition of the 42-residue amyloid beta protein (Abeta) in brain regions serving memory and cognition. In animal models of AD, immunization with Abeta results in the clearance of Abeta deposits from the brain. However, a trial of vaccination with synthetic human Abeta1-42 in AD resulted in the development of meningoencephalitis in some patients. We measured cellular immune responses to Abeta in middle-aged and elderly healthy subjects and in patients with AD. A significantly higher proportion of healthy elderly subjects and patients with AD had strong Abeta-reactive T cell responses than occurred in middle-aged adults. The immunodominant Abeta epitopes in humans resided in amino acids 16-33. Epitope mapping enabled the identification of MHC/T cell receptor (TCR) contact residues. The occurrence of intrinsic T cell reactivity to the self-antigen Abeta in humans has implications for the design of Abeta vaccines, may itself be linked to AD susceptibility and course, and appears to be associated with the aging process.
阿尔茨海默病（AD）的特征是在负责记忆和认知的脑区中42个氨基酸残基的β淀粉样蛋白（Aβ）进行性沉积。在AD动物模型中，用Aβ免疫可导致脑内Aβ沉积物的清除。然而，一项在AD患者中使用合成人Aβ1-42进行疫苗接种的试验导致部分患者发生了脑膜脑炎。我们检测了中年和老年健康受试者以及AD患者对Aβ的细胞免疫反应。与中年成年人相比，健康老年受试者和AD患者中具有强烈Aβ反应性T细胞反应的比例显著更高。人类免疫显性Aβ表位位于氨基酸16-33。表位作图能够鉴定主要组织相容性复合体/ T细胞受体（TCR）接触残基。人类对自身抗原Aβ存在内在T细胞反应性，这对Aβ疫苗的设计具有影响，可能本身与AD易感性和病程相关，并且似乎与衰老过程有关。
