Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322.
School of Medicine, Emory University, Atlanta, GA 30322; and.
J Immunol. 2018 Jul 1;201(1):19-30. doi: 10.4049/jimmunol.1800295. Epub 2018 May 18.
TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors and form memory. However, in the context of chronic infections, it is unclear what the overall profile of TCR affinity for Ag is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the two-dimensional micropipette adhesion frequency assay and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IA GP-specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) lymphocytic choriomeningitis virus infection. In each response, we show CD4 T cell population affinity peaks at the effector phase and declines with memory. Of interest, the range and average relative two-dimensional affinity was equivalent between acute and chronic infection, indicating chronic Ag exposure did not skew TCR affinity. In contrast, functional and tetramer avidity measurements revealed divergent results and lacked a consistent correlation with TCR affinity. Our findings highlight that the immune system maintains a diverse range in TCR affinity even under the pressures of chronic Ag stimulation.
T 细胞受体（TCR）对肽-MHC 的亲和力决定了 T 细胞的功能效率及其向效应细胞分化和形成记忆的倾向。然而，在慢性感染的情况下，尚不清楚 Ag 的 TCR 亲和力的整体特征是什么，以及它是否与急性感染不同。我们使用二维微管附着频率测定法提供的综合亲和力分析，以及 MHC Ⅱ类四聚体和功能亲和力的常见间接亲和力评估方法，在急性（Armstrong）和慢性（克隆 13）淋巴细胞脉络丛脑膜炎病毒感染的小鼠模型中跟踪了 IA GP 特异性细胞。在每个反应中，我们都显示出 CD4 T 细胞群体的亲和力在效应期达到峰值，并随着记忆的形成而下降。有趣的是，急性和慢性感染之间的二维亲和力范围和平均相对亲和力相当，这表明慢性 Ag 暴露并没有使 TCR 亲和力发生偏斜。相比之下，功能和四聚体亲和力测量结果显示出不同的结果，并且与 TCR 亲和力缺乏一致的相关性。我们的研究结果表明，即使在慢性 Ag 刺激的压力下，免疫系统也能保持 TCR 亲和力的多样性。
