Here is the actual paper:
Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4[SUP]+[/SUP] T-cell response with pre-primed responses directed against common cold coronaviruses
Tim Westphal[SUP]1,2[/SUP]
Maria Mader[SUP]1[/SUP]
Hendrik Karsten[SUP]1[/SUP]
Leon Cords[SUP]1[/SUP]
Maximilian Knapp[SUP]1[/SUP]
Sophia Schulte[SUP]1[/SUP]
Lennart Hermanussen[SUP]1[/SUP]
Sven Peine[SUP]3[/SUP]
Vanessa Ditt[SUP]3[/SUP]
Alba Grifoni[SUP]4[/SUP]
Marylyn Martina Addo[SUP]1,2,5,6[/SUP]
Samuel Huber[SUP]1[/SUP]
Alessandro Sette[SUP]4[/SUP]
Marc Lütgehetmann[SUP]2,7[/SUP]
Sven Pischke[SUP]1,2[/SUP]
William W. Kwok[SUP]8[/SUP]
John Sidney[SUP]4[/SUP]
Julian Schulze zur Wiesch[SUP]1,2*[/SUP]
- [SUP]1[/SUP]Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- [SUP]2[/SUP]German Center for Infection Research Deutsches Zentrum für Infektionsforschung (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
- [SUP]3[/SUP]Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- [SUP]4[/SUP]Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- [SUP]5[/SUP]Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
- [SUP]6[/SUP]Institute of Infection Research and Vaccine Development, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- [SUP]7[/SUP]Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- [SUP]8[/SUP]Benaroya Research Institute at Virginia Mason, Seattle, WA, United States
Introduction: The nonstructural protein 12 (NSP12) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has a high sequence identity with common cold coronaviruses (CCC).
Methods: Here, we comprehensively assessed the breadth and specificity of the NSP12-specific T-cell response after
in vitro T-cell expansion with 185 overlapping 15-mer peptides covering the entire SARS-CoV-2 NSP12 at single-peptide resolution in a cohort of 27 coronavirus disease 2019 (COVID-19) patients. Samples of nine uninfected seronegative individuals, as well as five pre-pandemic controls, were also examined to assess potential cross-reactivity with CCCs.
Results: Surprisingly, there was a comparable breadth of individual NSP12 peptide-specific CD4[SUP]+[/SUP] T-cell responses between COVID-19 patients (mean: 12.82 responses; range: 0–25) and seronegative controls including pre-pandemic samples (mean: 12.71 responses; range: 0–21). However, the NSP12-specific T-cell responses detected in acute COVID-19 patients were on average of a higher magnitude. The most frequently detected CD4[SUP]+[/SUP] T-cell peptide specificities in COVID-19 patients were aa236–250 (37%) and aa246–260 (44%), whereas the peptide specificities aa686–700 (50%) and aa741–755 (36%), were the most frequently detected in seronegative controls. In CCC-specific peptide-expanded T-cell cultures of seronegative individuals, the corresponding SARS-CoV-2 NSP12 peptide specificities also elicited responses
in vitro. However, the NSP12 peptide-specific CD4[SUP]+[/SUP] T-cell response repertoire only partially overlapped in patients analyzed longitudinally before and after a SARS-CoV-2 infection.
Discussion: The results of the current study indicate the presence of pre-primed, cross-reactive CCC-specific T-cell responses targeting conserved regions of SARS-CoV-2, but they also underline the complexity of the analysis and the limited understanding of the role of the SARS-CoV-2 specific T-cell response and cross-reactivity with the CCCs.
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1182504/full
