Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans
Description
Abstract:
SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.
More Information:
- Preprint: Research Square.
- Sample information: data_inventory.csv file.
- Code code_github_repo.zip or at the original github repo
- Interactive Portal: CellPilot
Files
code_github_repo.zip
Additional details
Funding
- Cancer Center Support Grant P30 CA091842
- National Institute of Health
- Programming durable immune responses to vaccination U01AI141990
- National Institute of Health
Dates
- Created
-
2023-12-04
- Updated
-
2024-05-30Released per publication