RESISTANCE TO HERPES STROMAL KERATITIS CONFERRED BY AN IGG2A-DERIVED PEPTIDE
RESISTANCE TO HERPES STROMAL KERATITIS CONFERRED BY AN IGG2A-DERIVED PEPTIDE
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DOI：
10.1038/376431a0
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发表时间：
1995-08-03
期刊：
影响因子：
64.8
通讯作者：
CANTOR, H
中科院分区：
文献类型：
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作者：
AVERY, AC;ZHAO, ZS;CANTOR, H
并非所有外周组织抗原都会进入胸腺，而且免疫系统如何对这类自身抗原保持耐受尚不清楚。由于对自身肽的耐受会在针对交叉反应性外来抗原的T细胞库中产生缺口（1,2），我们研究了这种机制是否也可能减少对外周组织所表达的相似肽的自身免疫反应。单纯疱疹性角膜基质炎（HSK）是一种由病毒诱导的、由T细胞介导的针对角膜组织的自身免疫反应（3 - 5），是人类失明的主要原因之一（6）。小鼠对HSK的抵抗力与免疫球蛋白基因的同种异型变异有关（7,8），可能是因为循环的免疫球蛋白衍生肽能够使针对角膜组织自身抗原的T细胞产生交叉耐受。在此我们表明，HSK是由针对角膜自身抗原的特异性T细胞克隆介导的，这些克隆也能识别一种源自IgG2a的带有同种异型的肽，而且使易患HSK的小鼠接触这种肽的可溶性形式可使其对HSK产生抵抗力。隔离组织蛋白和循环蛋白之间肽亚序列的共同表达对于维持自身耐受和预防自身免疫可能很重要。
NOT all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens(1,2), we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells(3-5), and is a leading cause of human blindness(6). Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes(7,8), possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.