Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, UT 84121, USA.
Immunity. 2013 Sep 19;39(3):508-20. doi: 10.1016/j.immuni.2013.08.033.
During CD4⁺ T cell activation, T cell receptor (TCR) signals impact T cell fate, including recruitment, expansion, differentiation, trafficking, and survival. To determine the impact of TCR signals on the fate decision of activated CD4⁺ T cells to become end-stage effector or long-lived memory T helper 1 (Th1) cells, we devised a deep-sequencing-based approach that allowed us to track the evolution of TCR repertoires after acute infection. The transition of effector Th1 cells into the memory pool was associated with a significant decrease in repertoire diversity, and the major histocompatibility complex (MHC) class II tetramer off rate, but not tetramer avidity, was a key predictive factor in the representation of individual clonal T cell populations at the memory stage. We conclude that stable and sustained interactions with antigens during the development of Th1 responses to acute infection are a determinative factor in promoting the differentiation of Th1 memory cells.
在 CD4⁺T 细胞激活过程中,T 细胞受体(TCR)信号影响 T 细胞的命运,包括募集、扩增、分化、归巢和存活。为了确定 TCR 信号对激活的 CD4⁺T 细胞命运决定的影响,使其成为终末效应或长寿记忆性辅助性 T 细胞 1(Th1)细胞,我们设计了一种基于深度测序的方法,该方法允许我们在急性感染后追踪 TCR 库的演变。效应 Th1 细胞向记忆池的转化与 repertoire 多样性的显著下降以及主要组织相容性复合物(MHC)II 类四聚体的脱离率有关,但不是四聚体亲和力,是在记忆阶段代表个体克隆 T 细胞群体的关键预测因子。我们的结论是,在急性感染时 Th1 反应中抗原的稳定和持续相互作用是促进 Th1 记忆细胞分化的决定性因素。