Multimodal characterization of antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection.

Zhang, B.; Upadhyay, R.; Hao, Y.; Samanovic, M. I.; Herati, R. S.; Blair, J.; Axelrad, J.; Mulligan, M. J.; Littman, D. R.; Satija, R.

doi:10.1101/2023.01.24.525203

bioRxiv · 10.1101/2023.01.24.525203

Multimodal characterization of antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection.

Zhang, B.·Upadhyay, R.·Hao, Y.·Samanovic, M. I.·Herati, R. S.·Blair, J.·Axelrad, J.·Mulligan, M. J.·Littman, D. R.·Satija, R.

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Abstract

The human immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we utilize multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after BNT162b2 immunization. Our data reveal distinct subpopulations of CD8+ T cells which reliably appear 28 days after prime vaccination (7 days post boost). Using a suite of cross-modality integration tools, we define their transcriptome, accessible chromatin landscape, and immunophenotype, and identify unique biomarkers within each modality. By leveraging DNA-oligo-tagged peptide-MHC multimers and T cell receptor sequencing, we demonstrate that this vaccine-induced population is SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we also identify these CD8+ populations in scRNA-seq datasets from COVID-19 patients and find that their relative frequency and differentiation outcomes are predictive of subsequent clinical outcomes. Our work contributes to our understanding of T cell immunity, and highlights the potential for integrative and multimodal analysis to characterize rare cell populations.

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Zhang, B., Upadhyay, R., Hao, Y., Samanovic, M. I., Herati, R. S., Blair, J., Axelrad, J., Mulligan, M. J., Littman, D. R., Satija, R.. 2023-01-24. Multimodal characterization of antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection.. https://doi.org/10.1101/2023.01.24.525203

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