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HLA-E-四聚合物排序的CD8+T细胞具有多样化的TCR谱

Linda Voogd¹, Anne M H F Drittij¹, Calinda K E Dingenouts¹

¹Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.

|March 5, 2024

概括

识别HLA-E的捐赠者不受限制的T细胞具有多样化的T细胞受体 (TCR) 谱. 即使T细胞对Mycobacterium tuberculosis (Mtb) 具有特异性,也观察到这种多样性,个人之间没有发现保存.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

人类白细胞抗原-E (HLA-E) 向自然杀手 (NK) 和T细胞呈现.
识别HLA-E的T细胞因有限的HLA-E等位变异而被称为无限制的供体T细胞.
对于HLA-E特异性T细胞受体 (TCRs) 的组成和谱系,仍然基本上是未知的.

研究的目的:

为了研究 CD8+ T 细胞的 TCR 谱,识别 HLA-E 与 Mycobacterium 结核病 (Mtb) 一起呈现.
为了确定在对特定的HLA-E-Mtb复合体作出反应的个体中是否存在TCR谱中的保存.

主要方法:

在21个个体的CD8+T细胞上进行TCR测序.
精选的HLA-E Mtb四聚体阳性 (TM+) 和阴性 (TM-) CD8+ T细胞.
在排序的T细胞上进行大量RNA测序和单细胞TCR测序.

主要成果:

确定的TCR曲目非常多样化.
在个体之间或个体内没有观察到TCRs的显著保存.
选择的TCRs在HLA-E/刺激时表现出激活,尽管不强大,但表明潜在的弱相互作用.

结论:

特定于HLA-E-Mtb的T细胞具有非常多样化的TCR谱.
缺乏TCR保护突显了针对特定HLA-E复合体的免疫反应的异质性.
需要进一步的研究来了解这些弱的TCR-HLA-E相互作用的功能影响.

关键词:

基因型定制是指基因型定制.免疫学免疫学免疫学文字转录学 (Transcriptomics) 是一个学科.

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