Knowlden Zackery A G, Sant Andrea J
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Sci Rep. 2016 Jun 22;6:28287. doi: 10.1038/srep28287.
Follicular helper T cells (Tfh) are essential for B cell production of high-affinity, class-switched antibodies. Much interest in Tfh development focuses on the priming environment of CD4 T cells. Here we explored the role that peptide specificity plays in the partitioning of the polyclonal CD4 T cell repertoire between Tfh and NonTfh lineages during the response to influenza. Surprisingly, we found that CD4 T cells specific for different epitopes exhibited distinct tendencies to segregate into Tfh or NonTfh. To alter the microenvironment and abundance, viral antigens were introduced as purified recombinant proteins in adjuvant as native proteins. Also, the most prototypical epitopes were expressed in a completely foreign protein. In many cases, the epitope-specific response patterns of Tfh vs. NonTfh persisted. The functional TcR avidity of only a subset of epitope-specific cells correlated with the tendency to drive a Tfh response. Thus, we conclude that in a polyclonal CD4 T cell repertoire, features of TcR-peptide:MHC class II complex have a strong deterministic influence on the ability of CD4 T cells to become a Tfh or a NonTfh. Our data is most consistent with at least 2 checkpoints of Tfh selection that include both TcR affinity and B cell presentation.
滤泡辅助性T细胞（Tfh）对于B细胞产生高亲和力、类别转换抗体至关重要。对Tfh发育的诸多研究兴趣集中在CD4 T细胞的启动环境上。在此，我们探讨了在对流感的应答过程中，肽特异性在多克隆CD4 T细胞库在Tfh和非Tfh谱系之间的分配中所起的作用。令人惊讶的是，我们发现针对不同表位的CD4 T细胞表现出不同的倾向，即分别分化为Tfh或非Tfh。为了改变微环境和丰度，将病毒抗原作为纯化的重组蛋白与佐剂一起作为天然蛋白引入。此外，最典型的表位在一种完全异源的蛋白中表达。在许多情况下，Tfh与非Tfh的表位特异性应答模式持续存在。只有一部分表位特异性细胞的功能性T细胞受体亲和力与驱动Tfh应答的倾向相关。因此，我们得出结论，在多克隆CD4 T细胞库中，T细胞受体 - 肽：MHC II类复合物的特征对CD4 T细胞成为Tfh或非Tfh的能力具有强大的决定性影响。我们的数据与至少两个Tfh选择检查点最为一致，这两个检查点包括T细胞受体亲和力和B细胞呈递。
