CD4 T cell affinity diversity is equally maintained during acute and chronic infection Chronic infection fails to alter T cell affinity diversity

摘要

T cell receptor (TCR) affinity for peptide major histocompatibility complex (pMHC) 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 antigen is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the 2-dimensional (2D) micropipette adhesion frequency assay (2D-MP) and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IA^b GP61–80 specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) LCMV 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 2D affinity was equivalent between acute and chronic infection, indicating chronic antigen 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 the immune system maintains a diverse range in TCR affinity even under the pressures of chronic antigen stimulation.