αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell-related features.
αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell-related features.
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来自多发性硬化症脑病变的αβT细胞受体显示与MAIT细胞相关的特征。
DOI：
10.1212/nxi.0000000000000107
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Dornmair K
中科院分区：
文献类型：
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作者：
Held K;Bhonsle-Deeng L;Siewert K;Sato W;Beltrán E;Schmidt S;Rühl G;Ng JK;Engerer P;Moser M;Klinkert WE;Babbe H;Misgeld T;Wekerle H;Laplaud DA;Hohlfeld R;Dornmair K
描述多发性硬化（MS）病变中聚集的T细胞表型，比较外周血T细胞亚群的病变T细胞受体（TCR）库，并从我们随访18年的索引患者的单个CD 8 + T细胞中鉴定成对的α和β链。我们结合免疫组织化学、激光显微切割和单细胞多重PCR来表征T细胞亚型，并从冷冻脑切片中的单个脑浸润T细胞中鉴定成对的TCRα和TCRβ链。通过焦磷酸测序分析病灶和外周TCR库。我们发现，临床发作时在活动性脑病变中显著扩增的TCR Vβ1+ T细胞群包含几个表达不同但密切相关的Vα7.2+ α链的亚克隆，包括粘膜相关不变T（MAIT）细胞的典型Vα7.2-Jα33链。其他三种α链在其抗原识别、高变互补决定区3中具有惊人的相似性。纵向库研究显示，发作时在脑中大量扩增的TCR链在血液或CSF中持续数年，但随后消失，除了典型的Vα7.2+ MAIT细胞和18年后仍在血液中可检测到的少数其他TCR序列。我们观察到大量扩增的TCR Vβ1-Jβ2.3链与不同但密切相关的典型或非典型MAIT细胞相关α链配对，这强烈表明早期活动性MS脑病变中存在抗原驱动的过程。
To characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8+ T cells from an index patient who we followed for 18 years. We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing. We found that a TCR Vβ1+ T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2+ α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the canonical Vα7.2+ MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years. Our observation that a massively expanded TCR Vβ1-Jβ2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell–related α chains strongly points to an antigen-driven process in early active MS brain lesions.