分子模拟与微生物、自身免疫交叉识别以及肿瘤免疫治疗
胡 兵1,2,魏于全1*
1四川大学华西医院人类疾病生物治疗教育部重点实验室及肿瘤中心,成都 610041;2国家人类基因组南方研究中心,上海 201203

摘 要:摘 要:分子模拟是生物界广为存在的一种自然现象。细菌等病原微生物可利用蛋白质序列或结构的相似而模拟宿主细胞某些分子的功能,从而协助其入侵与存活;另一方面,微生物也可因某些蛋白质的同源或相似而致宿主交叉免疫反应,导致自身免疫参与自身免疫疾病的发生,其本质是一种交叉识别。本室及其他研究小组发现可利用不同种属某些肿瘤相关同源分子的异源性激发特异的免疫反应,并因其同源性而交叉反应于宿主分子,从而产生抗肿瘤的自身免疫,亦即通过异种同源分子的策略主动免疫治疗肿瘤。这种模拟还可以在表位肽的水平进行,相信分子模拟的深入研究将有助于揭示进化与分子识别的本质以及自身免疫的规律,从而探索分子模拟在疾病预防与治疗中的应用。
关键词:分子模拟;微生物;自身免疫;肿瘤免疫治疗

Molecular mimicry associated with infection, autoimmunity, and tumor immunotherapy
HU Bing1,2, WEI Yu-Quan1*
1 Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, China, and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China; 2 Chinese National Human Genome Center at Shanghai, Shanghai 201203, China

Abstract: Abstract: Pathogens have developed sophisticated adaptations to achieve their own goal during the history of evolution. They could mimicry the function of ligands of host cellular surface receptors or other proteins to adhere and invade by sequence or structure similarity. On the other hand, pathogens with proteins that is immunologically similar to host autoantigen but differ sufficiently to be immunogenic, could break down the immune tolerance to host autoantigen by cross-reaction of the induced immune responses. The myelin basic protein is one of identified and well-characterized autoantigen homologue to some microbial agents, which could result in multiple sclerosis. Since most tumor associated antigens or carcinogenesis related key molecules are known as nonmutated normal self-proteins, our and other research groups have explored the molecular mimicry mechanism to cure tumors. It{$39}s shown many xenogeneic homologous molecules corresponding to the tumor related proteins or epitope peptide that are synthetic but substituted some amino acid residues corresponding to self proteins could as an altered immunogen to induce immune responses that could cross-react with the original molecule and result in antitumor activity. Though there is still a long way to go, it can be predicted the study about molecular mimicry could provide insight into organism, evolution, autoimmunity disease and could be implicated to explore the clue for treat cancer.
Key words: molecular mimicry; infection; autoimmunity; tumor immunotherapy

Back to top