Assessment of SARS-CoV-2 specific CD4(+) and CD8 (+) T cell responses using MHC class I and II tetramers

Poluektov, Yuri; George, Marybeth; Daftarian, Pirouz; Delcommenne, Marc

doi:10.1016/j.vaccine.2021.03.008

Cited by 17 publications

(14 citation statements)

References 28 publications

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“…While SARS-CoV-2-specific CD8 + T-cells have already been phenotypically studied in this context [26][27][28][29], SARS-CoV-2-specific CD4 + T-cells have rarely been studied through major histocompatibility complex (MHC) multimer staining [30][31][32]. In particular, we lack data on the longitudinal ex vivo frequency and phenotype over the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Cords

Knapp

Woost

et al. 2022

Viruses

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Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4+ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4+ T-cell response in both patients, with higher frequencies of virus-specific CD4+ T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4+ T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4+ T-cells with CD45RA− CXCR5+ PD-1+ circulating T follicular helper cell (cTFH) phenotype. Furthermore, we observed a delayed contraction of CD127− virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4+ T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell—T-cell interaction, a robust virus-specific CD4+ T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.

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Section: Introductionmentioning

confidence: 99%

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Cords

Knapp

Woost

et al. 2022

Viruses

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“…SARS-CoV-2-derived peptides-loaded MHC class I (pMHCI) tetramers were generated by QuickSwitch TM Quant HLA-A*24:02 Tetramer Kit-PE (MBL International Corporation) according to an industrial instruction manual [ 22 ]. Briefly, 50 μL of tetramer folded with an irrelevant exchangeable peptide at 50 μg/mL was mixed with 1 μL of peptide at 1 mg/mL and 1 μL of Peptide Exchange Factor for 4 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Identification of cytotoxic T cells and their T cell receptor sequences targeting COVID-19 using MHC class I-binding peptides

et al. 2022

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Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) was first reported in China in December 2019, various variants have been identified in different areas of the world such as United Kingdom (alpha), South Africa (beta and omicron), Brazil (gamma), and India (delta). Some of SARS-CoV-2 variants, each of which is characterized by a unique mutation(s) in spike protein, are concerned due to their high infectivity and the capability to escape from neutralizing antibodies elicited by vaccinations. To identify peptide epitopes that are derived from SARS-CoV-2 viral proteins and possibly induce CD8+ T cell immunity, we investigated SARS-CoV-2-derived peptides that are likely to bind to major histocompatibility complex (MHC) class I molecules. We identified a total of 15 peptides that bind to human leukocyte antigen (HLA)-A*24:02, HLA-A*02:01, or HLA-A*02:06, and possibly induce cytotoxic T lymphocytes (CTLs); thirteen of them corresponded to ORF1ab polyprotein, one peptide to spike protein and the remaining one to membrane glycoprotein. CD8+ T cells that recognize these peptides were detected in peripheral blood samples in three individuals recovered from COVID-19 as well as non-infected individuals. Since most of these peptides are commonly conserved among other coronaviruses including SARS-CoV and/or MERS-CoV, these might be useful to maintain T cell responses to coronaviruses that are pandemic at present and will become the future threat. We could define pairs of TRA and TRB sequences of nine CTL clones that recognize SARS-CoV-2-derived peptides. We might use these SARS-CoV-2-derived peptide-reactive TCR sequences for investigating the history of SARS-CoV-2 infection.

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“…Where available, references for certain HLA restrictions from previous studies were also included. [50][51][52][53] These results suggest that several peptide specificities derived from the SARS-CoV-2 spike glycoprotein might be promiscuous HLA binders. The match of in vitro HLA binding data, response frequencies from our experiments and observations from previous studies hint towards defined HLA restrictions for several of these CD4 + T-cell epitopes.…”

Section: Epitope Distribution Within the Sars-cov-2 Spike Glycoproteinmentioning

confidence: 83%

“…Where available, references for certain HLA restrictions from previous studies were also included. 50 , 51 , 52 , 53 …”

Section: Resultsmentioning

confidence: 99%

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High‐resolution analysis of individual spike peptide‐specific CD4⁺ T‐cell responses in vaccine recipients and COVID‐19 patients

et al. 2022

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Objectives Potential differences in the breadth, distribution and magnitude of CD4 + T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level. Methods Following virus‐specific in vitro cultivation, we determined the T‐cell responses directed against 253 individual overlapping 15‐mer peptides covering the entire SARS‐CoV‐2 spike glycoprotein using IFN‐γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides. Results We mapped 955 single peptide‐specific CD4 + T‐cell responses in a cohort of COVID‐19 patients ( n = 8), uninfected vaccinees ( n = 16) and individuals who experienced both infection and vaccination ( n = 11). Patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4 + T‐cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN‐γ CD4 + T‐cell responses was observed in COVID‐19 patients (median 0.35%), and three‐time vaccinees showed a higher magnitude than two‐time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides. Conclusion Both SARS‐CoV‐2 infection and vaccination prime broadly directed T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein. This comprehensive high‐resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike‐specific T‐cell responses.

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Assessment of SARS-CoV-2 specific CD4(+) and CD8 (+) T cell responses using MHC class I and II tetramers

Cited by 17 publications

References 28 publications

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Identification of cytotoxic T cells and their T cell receptor sequences targeting COVID-19 using MHC class I-binding peptides

High‐resolution analysis of individual spike peptide‐specific CD4⁺ T‐cell responses in vaccine recipients and COVID‐19 patients

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Assessment of SARS-CoV-2 specific CD4(+) and CD8 (+) T cell responses using MHC class I and II tetramers

Cited by 17 publications

References 28 publications

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Identification of cytotoxic T cells and their T cell receptor sequences targeting COVID-19 using MHC class I-binding peptides

High‐resolution analysis of individual spike peptide‐specific CD4+ T‐cell responses in vaccine recipients and COVID‐19 patients

Contact Info

Product

Resources

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High‐resolution analysis of individual spike peptide‐specific CD4⁺ T‐cell responses in vaccine recipients and COVID‐19 patients