CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans

• Published in: Nature immunology Vol. 25; no. 9; pp. 1731 - 1741
• Main Authors: Borcherding, Nicholas, Kim, Wooseob, Quinn, Michael, Han, Fangjie, Zhou, Julian Q., Sturtz, Alexandria J., Schmitz, Aaron J., Lei, Tingting, Schattgen, Stefan A., Klebert, Michael K., Suessen, Teresa, Middleton, William D., Goss, Charles W., Liu, Chang, Crawford, Jeremy Chase, Thomas, Paul G., Teefey, Sharlene A., Presti, Rachel M., O’Halloran, Jane A., Turner, Jackson S., Ellebedy, Ali H., Mudd, Philip A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 20.08.2024; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1270; 631/250/1620/1616; 631/250/2520; 631/250/255/2514; 631/250/590/2293; Biomedical and Life Sciences; Biomedicine; Blood; CD4 antigen; Coronaviruses; COVID-19; Deep learning; Epitope mapping; Germinal centers; Immunization; Immunology; Infections; Infectious Diseases; Lymph nodes; Lymphatic drainage; Lymphatic system; Lymphocytes; Lymphocytes T; Phenotypes; Resource; Severe acute respiratory syndrome coronavirus 2; Spike protein; Transcriptomics
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-024-01888-9

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4 + T cell responses. Using single-cell transcriptomics, here, we evaluated CD4 + T cells specific for the SARS-CoV-2 spike protein in the blood and draining lymph nodes (dLNs) of individuals 3 months and 6 months after vaccination with the BNT162b2 mRNA vaccine. We analyzed 1,277 spike-specific CD4 + T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity. Human dLN spike-specific CD4 + follicular helper T (T FH ) cells exhibited heterogeneous phenotypes, including germinal center CD4 + T FH cells and CD4 + IL-10 + T FH cells. Analysis of an independent cohort of SARS-CoV-2-infected individuals 3 months and 6 months after infection found spike-specific CD4 + T cell profiles in blood that were distinct from those detected in blood 3 months and 6 months after BNT162b2 vaccination. Our findings provide an atlas of human spike-specific CD4 + T cell transcriptional phenotypes in the dLNs and blood following SARS-CoV-2 vaccination or infection. Mudd, Ellebedy and colleagues integrate single-cell transcriptomics and TCR sequencing to characterize the spike-specific CD4 + T FH cell response in the lymph nodes and blood of BNT162b2-vaccinated and SARS-CoV-2-infected individuals up to 6 months after vaccination or infection.