Ryan Kelli R, Patel Sarju D, Stephens Leigh A, Anderton Stephen M
University of Edinburgh, Institute of Immunology and Infection Research, School of Biological Sciences, Kings Buildings, West Mains Road, Edinburgh, EH9 3JT, UK.
J Autoimmun. 2007 Dec;29(4):262-71. doi: 10.1016/j.jaut.2007.07.014. Epub 2007 Sep 17.
Extensive cross-reactivity in T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes seems to be essential to give sufficient immune surveillance against invading pathogens. This carries with it an inherent risk that T cells activated during a response to clear an infection can, perhaps years later, respond to a self pMHC of sufficient similarity. This lies at the heart of the molecular mimicry theory. Here we discuss our studies on the disease-causing potential of altered peptide ligands (APL) based on the sequence of a single autoantigenic epitope, the Ac1-9 peptide of myelin basic protein that induces experimental autoimmune encephalomyelitis in mice. These show that the window of similarity to self for induction of disease by cross-reactive non-self peptides is actually quite restricted. We show that each of the three pillars of immune tolerance (death, anergy/adaptation and regulation) has a role in limiting the risk of molecular mimicry by maintaining a threshold for harm.
T细胞受体（TCR）对肽-主要组织相容性复合体（pMHC）复合物的广泛交叉反应性似乎对于提供针对入侵病原体的充分免疫监视至关重要。这带来了一种内在风险，即在清除感染的反应过程中被激活的T细胞，可能在数年之后，会对具有足够相似性的自身pMHC产生反应。这是分子模拟理论的核心所在。在此，我们讨论基于单个自身抗原表位（髓鞘碱性蛋白的Ac1-9肽，可在小鼠中诱发实验性自身免疫性脑脊髓炎）序列的改变肽配体（APL）致病潜力的研究。这些研究表明，交叉反应性非自身肽诱导疾病与自身相似性的窗口实际上相当狭窄。我们表明，免疫耐受的三大支柱（死亡、无反应性/适应性和调节）在通过维持危害阈值来限制分子模拟风险方面均发挥作用。
