SCI
18 September 2024
A mass cytometry method pairing T cell receptor and differentiation state analysis
(Nat Immunol; IF:27.7)
Garcia Castillo J, DeBarge R, Mende A, Tenvooren I, Marquez DM, Straub A, Busch DH, Spitzer MH, DuPage M: A mass cytometry method pairing T cell receptor and differentiation state analysis. Nat Immunol 2024, 25(9):1754-1763.
Correspondence to: matthew.spitzer@ucsf.edu; dupage@berkeley.edu
T cell antigen receptor (TCR) recognition followed by clonal expansion is a fundamental feature of adaptive immune responses. Here, we present a mass cytometric (CyTOF) approach to track T cell responses by combining antibodies for specific TCR Vα and Vβ chains with antibodies against T cell activation and differentiation proteins in mice. This strategy identifies expansions of CD8+ and CD4+ T cells expressing specific Vβ and Vα chains with varying differentiation states in response to Listeria monocytogenes, tumors and respiratory influenza infection. Expanded T cell populations expressing Vβ chains could be directly linked to the recognition of specific antigens from Listeria, tumor cells or influenza. In the setting of influenza infection, we found that common therapeutic approaches of intramuscular vaccination or convalescent serum transfer altered the TCR diversity and differentiation state of responding T cells. Thus, we present a method to monitor broad changes in TCR use paired with T cell phenotyping during adaptive immune responses.
T细胞抗原受体(T cell antigen receptor, TCR)识别和克隆扩增是适应性免疫应答的基本特征。在这里，我们提出了一种质谱流式细胞分析(CyTOF)方法，通过结合针对特异性TCR Vα和Vβ链的抗体和针对T细胞活化和分化蛋白的抗体来追踪小鼠的T细胞应答。该策略确定了表达不同分化状态的特异性Vβ和Vα链的CD8+和CD4+ T细胞在单核细胞增生性李斯特菌、肿瘤和呼吸道流感感染后的扩增。表达Vβ链的扩增T细胞群可能与识别李斯特菌、肿瘤细胞或流感的特异性抗原直接相关。在流感感染的情况下，我们发现肌肉注射疫苗或恢复期血清转移等常见治疗方法改变了应答T细胞的TCR多样性和分化状态。因此，我们提出了一种监测适应性免疫应答期间与T细胞表型配对的TCR使用的广泛变化的方法。
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