MINIMUM STRUCTURAL REQUIREMENTS FOR PEPTIDE PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES - IMPLICATIONS IN INDUCTION OF AUTOIMMUNITY
MINIMUM STRUCTURAL REQUIREMENTS FOR PEPTIDE PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES - IMPLICATIONS IN INDUCTION OF AUTOIMMUNITY
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DOI：
10.1073/pnas.91.2.767
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发表时间：
1994-01-18
影响因子：
11.1
通讯作者：
MCDEVITT, HO
中科院分区：
文献类型：
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作者：
GAUTAM, AM;LOCK, CB;MCDEVITT, HO
对自身蛋白免疫耐受失败的确切机制尚不清楚。主要组织相容性复合体（MHC）易感性等位基因、靶肽和具有抗自身反应性的T细胞必须存在才能引起自身免疫性疾病。实验性自身免疫性脑脊髓炎（EAE）是一种人类自身免疫性疾病多发性硬化症的鼠模型。在EAE中，髓鞘碱性蛋白（MBP）的残基1-11是PL/J和（PL/J x SJL/J）F-1小鼠中的主要疾病诱导决定因素。在这里，我们报告，六个残基的肽（其中五个天然）的MBP可以诱导EAE。使用MBP-（1-11）肽的肽类似物，我们证明，只有四个天然MBP残基需要刺激MBP特异性T细胞。因此，本研究证明了MHC II类分子有效抗原呈递的最低结构要求较低。许多病毒和细菌蛋白质与宿主自身蛋白质共享短序列的氨基酸相似性，这种现象称为分子模拟。由于六个残基的肽可以使MBP特异性T细胞致敏以引起EAE，这些结果定义了自身免疫中分子模拟的最小序列同一性。
The precise mechanisms of failure of immunological tolerance to self proteins are not known. Major histocompatibility complex (MHC) susceptibility alleles, the target peptides, and T cells with anti-self reactivity must be present to cause autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a murine model of a human autoimmune disease, multiple sclerosis. In EAE, residues 1-11 of myelin basic protein (MBP) are the dominant disease-inducing determinants in PL/J and (PL/J x SJL/J)F-1 mice. Here we report that a six-residue peptide (five of them native) of MBP can induce EAE. Using peptide analogues of the MBP-(1-11) peptide, we demonstrate that only four native MBP residues are required to stimulate MBP-specific T cells. Therefore, this study demonstrates lower minimum structural requirements for effective antigen presentation by MHC class II molecules. Many viral and bacterial proteins;share short runs of amino acid similarity with host self proteins, a phenomenon known as molecular mimicry. Since a six-residue peptide can sensitize MBP-specific T cells to cause EAE, these results define a minimum sequence identity for molecular mimicry in autoimmunity.