Ludwig Center for Cancer Research, University of Lausanne, Lausanne CH-1011, Switzerland.
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15318-23. doi: 10.1073/pnas.1105419108. Epub 2011 Aug 29.
Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts.
个体 T 细胞具有不同的克隆起源，能够介导针对传染病和癌症的免疫保护。其功能受到严格调控，但尚未完全阐明。了解每个 T 细胞的作用将有助于基于 T 细胞反应的实验室评估来预测免疫保护。在这里，我们开发了直接在体外对单个 CD8 T 细胞进行分子和功能同时评估的技术。我们研究了两组接种两种密切相关的肿瘤抗原肽的黑色素瘤患者。接种疫苗诱导了具有强大记忆和效应功能的 T 细胞，几乎所有第一组患者的 T 细胞以及第二组患者的部分 T 细胞中都发现了这种情况。有趣的是，高功能性并不局限于优势克隆型。相反，优势和非优势克隆型都获得了同等的功能能力。与此同时，这也适用于 EBV 和 CMV 特异性 T 细胞。因此，非优势克隆型可能与优势克隆型一样为免疫做出贡献。
