Dynamics of the CD8+ T cell response to a model of acute viral infection (VIR4P.1017)

Abstract

Abstract During an acute viral infection T cells specific to viral antigens, as determined by the T-cell receptor (TCR), activate and expand. To determine the breadth of immune response to infection, and to understand recruitment to immunological memory, characterizing the TCR repertoire before, during, and after a model of acute viral infection is necessary. Here we use the yellow fever vaccine (YFV) to model acute viral infection. Blood was collected from 9 subjects at 0, 14, and 90 days after YFV administration. In addition to isolating PBMC for all time points, we sorted for YFV-specific effector T-cells at day 14 and for central and effector memory T-cells in 6 of 9 subjects at day 90. For each sample, gDNA was extracted and the TCR repertoire was assayed by high-throughput TCRβ sequencing. Expanded T cell clones can specifically bind a pathogen-derived epitope (specific), or receive proliferation signals without antigen-specificity (bystander). YFV-specific clones were identified by enrichment in the YFV-specific day 14 sort vs. day 14 PBMC; in each subject, we estimate that the antigen-specific immune response comprises approximately 103 T cell clones. Bystanders were identified as clones expanding from day 0 to day 14 PBMC that are not YFV-specific. Many more YFV-specific clones were recruited to memory at day 90 than bystander clones (40% vs. 3%), indicating that antigen specificity, rather than just proliferation, is a major determinant of memory recruitment.