Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses
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Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses. / Westphal, Tim; Mader, Maria; Karsten, Hendrik; Cords, Leon; Knapp, Maximilian; Schulte, Sophia; Hermanussen, Lennart; Peine, Sven; Ditt, Vanessa; Grifoni, Alba; Addo, Marylyn Martina; Huber, Samuel; Sette, Alessandro; Lütgehetmann, Marc; Pischke, Sven; Kwok, William W; Sidney, John; Schulze Zur Wiesch, Julian.
In: FRONT IMMUNOL, Vol. 14, 1182504, 2023.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses
AU - Westphal, Tim
AU - Mader, Maria
AU - Karsten, Hendrik
AU - Cords, Leon
AU - Knapp, Maximilian
AU - Schulte, Sophia
AU - Hermanussen, Lennart
AU - Peine, Sven
AU - Ditt, Vanessa
AU - Grifoni, Alba
AU - Addo, Marylyn Martina
AU - Huber, Samuel
AU - Sette, Alessandro
AU - Lütgehetmann, Marc
AU - Pischke, Sven
AU - Kwok, William W
AU - Sidney, John
AU - Schulze Zur Wiesch, Julian
N1 - Copyright © 2023 Westphal, Mader, Karsten, Cords, Knapp, Schulte, Hermanussen, Peine, Ditt, Grifoni, Addo, Huber, Sette, Lütgehetmann, Pischke, Kwok, Sidney and Schulze zur Wiesch.
PY - 2023
Y1 - 2023
N2 - 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+ 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+ 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+ 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.
AB - 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+ 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+ 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+ 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.
KW - Humans
KW - CD4-Positive T-Lymphocytes
KW - Common Cold
KW - COVID-19
KW - Peptides
KW - SARS-CoV-2
KW - T-Lymphocytes
U2 - 10.3389/fimmu.2023.1182504
DO - 10.3389/fimmu.2023.1182504
M3 - SCORING: Journal article
C2 - 37215095
VL - 14
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 1182504
ER -
