tetano
Editor, Senior Moderator
Front Immunol
. 2023 May 5;14:1182504.
doi: 10.3389/fimmu.2023.1182504. eCollection 2023. 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]
Affiliations
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.
Keywords: CD4+ T-cells; Cross-reactivities; NSP12; RNA-dependant RNA polymerase; SARS-CoV-2; common cold coronaviruses; epitope analysis; sequence identities.
. 2023 May 5;14:1182504.
doi: 10.3389/fimmu.2023.1182504. eCollection 2023. 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]
Affiliations
- PMID: 37215095
- PMCID: PMC10196118
- DOI: 10.3389/fimmu.2023.1182504
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.
Keywords: CD4+ T-cells; Cross-reactivities; NSP12; RNA-dependant RNA polymerase; SARS-CoV-2; common cold coronaviruses; epitope analysis; sequence identities.