HCMV-specific memory T cell clonotypes are phenotypically and functionally heterogeneous but stable over many years of latent infection 9373

Abstract Description Cytomegalovirus (CMV) is a betaherpesvirus that causes lifelong latent infection. Circulating CMV-specific memory T cells are responsible for keeping viral reactivation in check, and they are often studied as a model of T cell exhaustion due to their chronic antigen exposure. However, the process by which these cells evolve over time is still not well understood. This study aims to characterize the CMV-specific memory T cell population in a cohort of individuals who have donated multiple blood samples to the BRI Biorepository over the course of 5-12 years. Using scRNAseq, I have identified expanded CMV-specific T cell clonotypes, with dominant and sub-dominant clones, in each donor’s blood draws from many years apart. In addition to sequencing, I have interrogated differences in the clones’ functionality using a novel method called Functionally-Enriched TCR Sequencing. My results show that CMV-specific T cell clonotypes are transcriptionally and functionally heterogeneous, based on each clone’s antigen specificity and TCR affinity, but the relative dominance and phenotype of each clone is remarkably stable over timepoints up to 12 years apart. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)