Trost Brett, Lucchese Guglielmo, Stufano Angela, Bickis Mik, Kusalik Anthony, Kanduc Darja
Department of Computer Science; University of Saskatchewan; Saskatoon, Canada.
Self Nonself. 2010 Oct;1(4):328-334. doi: 10.4161/self.1.4.13315.
The hypothesis that mimicry between a self and a microbial peptide antigen is strictly related to autoimmune pathology remains a debated concept in autoimmunity research. Clear evidence for a causal link between molecular mimicry and autoimmunity is still lacking. In recent studies we have demonstrated that viruses and bacteria share amino acid sequences with the human proteome at such a high extent that the molecular mimicry hypothesis becomes questionable as a causal factor in autoimmunity. Expanding upon our analysis, here we detail the bacterial peptide overlapping to the human proteome at the penta-, hexa-, hepta- and octapeptide levels by exact peptide matching analysis and demonstrate that there does not exist a single human protein that does not harbor a bacterial pentapeptide or hexapeptide motif. This finding suggests that molecular mimicry between a self and a microbial peptide antigen cannot be assumed as a basis for autoimmune pathologies. Moreover, the data are discussed in relation to the microbial immune escape phenomenon and the possible vaccine-related autoimmune effects.
自身与微生物肽抗原之间的分子模拟与自身免疫性病理严格相关这一假说,在自身免疫性研究中仍是一个有争议的概念。分子模拟与自身免疫之间因果关系的明确证据仍然缺乏。在最近的研究中,我们已经证明病毒和细菌与人类蛋白质组共享氨基酸序列的程度如此之高,以至于分子模拟假说作为自身免疫的一个因果因素变得值得怀疑。在我们分析的基础上,这里我们通过精确的肽匹配分析,详细阐述了在五肽、六肽、七肽和八肽水平上与人类蛋白质组重叠的细菌肽,并证明不存在一种不含有细菌五肽或六肽基序的人类蛋白质。这一发现表明,自身与微生物肽抗原之间的分子模拟不能被假定为自身免疫性疾病的基础。此外,还讨论了与微生物免疫逃逸现象以及可能的疫苗相关自身免疫效应相关的数据。