Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, USA.
Nat Immunol. 2024 Sep;25(9):1754-1763. doi: 10.1038/s41590-024-01937-3. Epub 2024 Aug 27.
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 (TCR) 识别后克隆扩增是适应性免疫反应的一个基本特征。在这里，我们提出了一种通过将针对特定 TCR Vα 和 Vβ 链的抗体与针对 T 细胞激活和分化蛋白的抗体相结合，来利用质谱流式细胞术 (CyTOF) 追踪 T 细胞反应的方法，以在小鼠中进行研究。该策略可识别对李斯特菌、肿瘤和呼吸道流感感染作出反应的 CD8 和 CD4 T 细胞的扩增，这些细胞表达特定的 Vβ 和 Vα 链，并具有不同的分化状态。表达 Vβ 链的扩增 T 细胞群体可直接与李斯特菌、肿瘤细胞或流感的特定抗原识别相关联。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的治疗方法改变了应答 T 细胞的 TCR 多样性和分化状态。因此，我们提出了一种方法，可在适应性免疫反应过程中监测 TCR 使用的广泛变化，并结合 T 细胞表型进行分析。
