Human skin is colonized b T cells that recognize CD1a independently of lipid
Human skin is colonized b T cells that recognize CD1a independently of lipid
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DOI：
10.1172/jci140706
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发表时间：
2021-01-04
影响因子：
15.9
通讯作者：
Moody, D. Branch
中科院分区：
文献类型：
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作者：
Cotton, Rachel N.;Cheng, Tan-Yun;Moody, D. Branch
CD1a-自身反应性T细胞在皮肤病中起重要作用，但免疫优势的自身脂类抗原的特性及其识别模式尚未解决。在大多数型号中。MHC和CD1蛋白作为较小抗原的展示平台。在这里，我们发现CD1a四聚体在没有添加抗原的情况下对每个受试者的大T细胞库进行染色，约占皮肤T细胞的1%。四聚体与T细胞结合的机制不需要任何确定的抗原。与CD1a蛋白携带的大约100个脂类配体发生结合，但可以与某些天然自身脂类向上或向下调节。TCR识别被映射到远离抗原出口入口的CD1a的外部A屋顶，解释了TCR如何结合可乐而不是携带脂质。因此，体内CD1a T细胞自身反应性的一个主要抗原靶点是CD1a本身。基于其在捐献者中的高频率和流行率，我们得出结论，CD1a特异性的、脂类无关的T细胞是人类皮肤T细胞库中的正常组成部分。CD1a四聚体不需要选择抗原和效应分子，是一种简单的方法，可以从组织和任何临床疾病中追踪这种CD1a特异性T细胞。
CD1a-autoreactive T cells contribute to skin disease, but the identity of immunodominant self-lipid antigens and their mode of recognition are not yet solved. In most models. MHC and CD1 proteins serve as display platforms for smaller antigens. Here, we showed that CD1a tetramers without added antigen stained large T cell pools in every subject tested, accounting for approximately 1% of skin T cells. The mechanism of tetramer binding to T cells did not require any defined antigen. Binding occurred with approximately 100 lipid ligands carried by CD1a proteins, but could be tuned upward or downward with certain natural self-lipids. TCR recognition mapped to the outer A roof of CD1a at sites remote from the antigen exit portal, explaining how TCRs can bind COla rather than carried lipids. Thus, a major antigenic target of CD1a T cell autoreactivity in vivo is CD1a itself. Based on their high frequency and prevalence among donors, we conclude that CD1a-specific, lipid-independent T cells are a normal component of the human skin T cell repertoire. Bypassing the need to select antigens and effector molecules, CD1a tetramers represent a simple method to track such CD1a-specific T cells from tissues and in any clinical disease.