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Antigen-specific CD4(+) T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans

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...

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Detalles Bibliográficos
Autores principales: Mudd, Philip, Borcherding, Nicholas, Kim, Wooseob, Quinn, Michael, Han, Fangjie, Zhou, Julian, Sturtz, Alexandria, Schmitz, Aaron, Lei, Tingting, Schattgen, Stefan, Klebert, Michael, Suessen, Teresa, Middleton, William, Goss, Charles, Liu, Chang, Crawford, Jeremy, Thomas, Paul, Teefey, Sharlene, Presti, Rachel, O’Halloran, Jane, Turner, Jackson, Ellebedy, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543502/
https://www.ncbi.nlm.nih.gov/pubmed/37790414
http://dx.doi.org/10.21203/rs.3.rs-3304466/v1
Descripción
Sumario: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 (T(FH)) exhibited distinct phenotypes, including germinal center (GC)-T(FH) and IL-10(+) T(FH), 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.