Category: Immune monitoring
T cell receptor (TCR) convergence refers to the phenomenon whereby antigen-driven selection enriches for TCRs having shared antigen specificity but different nucleotide sequences. The extent to which convergence arises owing to chronic viral infection is not yet established. Here we sought to identify features of chronic cytomegalovirus (CMV) infection using TCRB profiling of peripheral blood (PBL) total RNA. Total RNA from PBL was obtained from 35 blood donors of known CMV status, then used for TCRB sequencing. Data were used to identify TCRB repertoire features correlated with CMV status. CMV-related convergence values are compared to convergent T cell responses in individuals with cancer treated with checkpoint inhibitors (CPI). T cell clone evenness was reduced in CMV positive individuals, predictive of CMV status (AUC=.86, p=2E-4, Wilcoxon), and strongly correlated between assays (Spearman cor=.96). TCR convergence was elevated in CMV positive individuals and uncorrelated with evenness (Spearman cor =-.03). Combination of convergence and evenness improved the performance of a logistic regression classifier (AUC= .93). CMV infection appears to significantly alter the T cell repertoire, suggesting that CMV status may be required for proper interpretation of T cell expansion in the context of CPI for cancer. TCR convergence may detect T cell responses to viral and tumor neoantigens and may serve as a useful biomarker for the identification of immunogenic tumors having few genetic alterations.