一种配对T细胞受体和分化状态分析的质谱流式细胞术方法。
A mass cytometry method pairing T cell receptor and differentiation state analysis.
发表日期：2024 Aug 27
作者：
Jesse Garcia Castillo, Rachel DeBarge, Abigail Mende, Iliana Tenvooren, Diana M Marquez, Adrian Straub, Dirk H Busch, Matthew H Spitzer, Michel DuPage
来源：
NATURE IMMUNOLOGY
摘要：
T 细胞抗原受体 (TCR) 识别和随后的克隆扩增是适应性免疫反应的基本特征。在这里，我们提出了一种质谱流式分析 (CyTOF) 方法，通过将特定 TCR Vα 和 Vβ 链的抗体与针对小鼠 T 细胞活化和分化蛋白的抗体相结合来跟踪 T 细胞反应。该策略识别了表达特定 Vβ 和 Vα 链的 CD8 和 CD4 T 细胞的扩增，这些细胞具有不同的分化状态，以响应单核细胞增多性李斯特菌、肿瘤和呼吸道流感感染。表达 Vβ 链的扩展 T 细胞群可能与李斯特菌、肿瘤细胞或流感的特定抗原的识别直接相关。在流感感染的情况下，我们发现肌内疫苗接种或恢复期血清转移等常见治疗方法改变了 TCR 多样性和应答 T 细胞的分化状态。因此，我们提出了一种在适应性免疫反应期间监测 TCR 使用与 T 细胞表型配对的广泛变化的方法。© 2024。作者，获得 Springer Nature America, Inc. 的独家许可。
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.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.