Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd NE, Atlanta Georgia, 30322, USA.
Nat Commun. 2016 Dec 15;7:13848. doi: 10.1038/ncomms13848.
A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only the highest-affinity T cells. Here we show the entire CD4+ T-cell repertoire, inclusive of low-affinity T cells missed by tetramers, using a T-cell receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors and expanded populations. In vivo limiting dilution assays reveal hundreds more precursor T cells than previously thought, with higher-affinity tetramer-positive T cells, comprising only 5-30% of the total antigen-specific naive repertoire. Lower-affinity T cells maintain their predominance as the primary immune response progresses, with no enhancement of survival of T cells with high-affinity TCRs. These findings demonstrate that affinity for antigen does not control CD4+ T-cell entry into the primary immune response, as a diverse range in affinity is maintained from precursor through peak of T-cell expansion.
已证实，使用 MHCII 肽四聚体鉴定的抗原特异性 T 细胞前体数量与强大的初始免疫应答相关。然而，这些四聚体仅能识别亲和力最高的 T 细胞。在此，我们使用 T 细胞受体（TCR）信号报告基因和微吸管分析来量化幼稚前体细胞和扩增群体，展示了整个 CD4+T 细胞库，包括四聚体错过的低亲和力 T 细胞。体内有限稀释分析显示，前体细胞的数量比之前认为的要多数百个，高亲和力四聚体阳性 T 细胞仅占总抗原特异性幼稚库的 5-30%。随着初始免疫应答的进展，低亲和力 T 细胞保持其优势，高亲和力 TCR 具有高 TCR 亲和力的 T 细胞的存活并没有增强。这些发现表明，抗原亲和力不能控制 CD4+T 细胞进入初始免疫应答，因为从前体细胞到 T 细胞扩增峰值，亲和力范围保持多样化。
