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通过单细胞RNA测序确定抗小鼠TCR单克隆抗体的基因组特异性

Genomic specificity of anti-mouse TCR mAbs determined by single-cell RNAseq.

作者信息

Magill Ian, Piekarsa Val, Kossida Sofia, Croteau Josh, Lee Amy, Balderas Robert, Zemmour David, Benoist Christophe

机构信息

Department of Immunology, Harvard Medical School, Boston, MA, United States.

International ImMunoGeneTics Information System, Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, France.

出版信息

J Immunol. 2025 Sep 1;214(9):2202-2210. doi: 10.1093/jimmun/vkaf094.

Abstract

T cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR variable regions was generated in the previous century. The separate identification of mAb-specific TCR-V proteins and TRV genes has resulted in multiple nomenclatures, making their relationships unclear. To formally re-establish this link and determine patterns of reactivity within TRV subfamilies, we sorted T cells from C57BL/6 mice positive for any one of a panel of 22 anti-V mAbs and determined their TRV genes by single-cell TCRseq. RNAseq data revealed consistently higher expression of repeated elements from the ERV1-family LTR RLTR6Mm (mapping to Gm20400) in cells utilizing TRBV segments encoded within a 66 kb genomic region between TRBV23 and TRBV30. Our findings provide a comprehensive resource for anti-mouse TCR mAb specificity and insight into V-gene usage biases and T cell function.

摘要

T细胞在免疫系统中发挥着关键作用,依靠其体细胞重排的T细胞受体(TCR)来识别肽-MHC复合物。上世纪产生了一套全面且广泛使用的针对TCR可变区的单克隆抗体(mAb)。mAb特异性TCR-V蛋白和TRV基因的分别鉴定导致了多种命名法,使得它们之间的关系不明确。为了正式重新建立这种联系并确定TRV亚家族内的反应模式,我们从C57BL/6小鼠中筛选出对22种抗V mAb中的任何一种呈阳性的T细胞,并通过单细胞TCRseq确定它们的TRV基因。RNAseq数据显示,在利用TRBV23和TRBV30之间66 kb基因组区域内编码的TRBV片段的细胞中,ERV1家族LTR RLTR6Mm(映射到Gm20400)的重复元件表达始终较高。我们的研究结果为抗小鼠TCR mAb特异性提供了全面的资源,并深入了解了V基因使用偏好和T细胞功能。

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