Optimization of antigen-specific CD8+ T cell activation conditions for infectious diseases including COVID-19

Xiao, Chanchan; Qiu, Congling; Deng, Jieping; Ye, Jiezhou; Gao, Lijuan; Su, Jun; Luo, Oscar Junhong; Wang, Pengcheng; Chen, Guobing

doi:10.1016/j.xpro.2021.100789

Cited by 7 publications

(8 citation statements)

References 3 publications

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“…Parameters were evaluated after 16 h and 7 days, respectively. On day 7, cells were re-stimulated with peptides for 6 h in the presence of GolgiPlug and GolgiStop (BD Cat#550583, Bedford, NY, USA) plus 50 IU ml −1 IL-2, and the production of IFN-γ was checked by intracellular FACS staining with anti-IFN-γ-PE (BioLegend Cat#506507, San Diego, California, USA) ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

CD8+ T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2

et al. 2022

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We identified SARS-CoV-2 specific antigen epitopes by HLA-A2 binding affinity analysis and characterized their ability to activate T cells. As the pandemic continues, variations in SARS-CoV-2 virus strains have been found in many countries. In this study, we directly assess the immune response to SARS-CoV-2 epitope variants. We first predicted potential HLA-A*02:01-restricted CD8+ T-cell epitopes of SARS-CoV-2. Using the T2 cell model, HLA-A*02:01-restricted T-cell epitopes were screened for their binding affinity and ability to activate T cells. Subsequently, we examined the identified epitope variations and analyzed their impact on immune response. Here, we identified specific HLA-A2-restricted T-cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides were confirmed to bind with HLA-A*02:01 and potentially be presented by antigen-presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. These epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytolytic activity toward target cells. Meanwhile, n-Sp1 epitope variant 5L>F significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A*02:01 and decreased proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SARS-CoV-2. Our data indicate that the variation of a dominant epitope will cause the deficiency of HLA-A*02:01 binding and T-cell activation, which subsequently requires the formation of a new CD8+ T-cell immune response in COVID-19 patients.

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Section: Methodsmentioning

confidence: 99%

CD8+ T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2

et al. 2022

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“…Our previous work has shown that the mutations in given CD8 + T cell epitopes resulted in antigen presentation deficiency and impaired antigen specific T cell function, indicating an immune evasion induced by viral evolution (Qiu et al, 2020;Xiao et al, 2021). In this work, we predicted the potential CD8 + T cell epitopes within the areas where these mutations are located, and compared the immune properties of the ancestral and mutant peptides, including MHC I binding and activation of CD8 + T cells.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response

et al. 2022

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“…The candidate peptides were synthesized by GenScript Biotechnology Co., Ltd. with purity >98% and resuspended in DMSO at a concentration of 10 mM. The titration of peptide concentration was performed as described previously 51 . The T2 cell line was shared by Anna Gil (University of Massachusetts Medical School).…”

Section: Methodsmentioning

confidence: 99%

“…T2 cells were seeded into 96-well plates and then incubated with peptides at a final concentration of 20 µM at 37 °C for 4 hours. DMSO was set as blank control; the reported HLA-A2-restricted influenza A M1 peptide (M58-66 GILGFVFTL) was set as positive control; and the validated EBV virus peptide (IVTDFSVIK) was set as negative control 26 , 27 , 51 . Cells were stained with PE anti-human HLA-A2 antibody (BioLegend, 343305) at 4 °C in the dark for 30 minutes and acquired on a FACSCanto flow cytometer (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults

et al. 2023

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Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

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Optimization of antigen-specific CD8+ T cell activation conditions for infectious diseases including COVID-19

Cited by 7 publications

References 3 publications

CD8+ T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2

CD8+ T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2

SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response

Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults

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