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

Qiu, Congling; Wang, Zhigang; Xiao, Chanchan; Chen, Xiongfei; Gao, Lijuan; Den, Jieping; Su, Jun; Su, Huanxing; Fang, Evandro Fei; Zhang, Zhang-Jin; Zhu, Guodong; Zhang, Jikai; Xie, Caojun; Yuan, Jun; Luo, Oscar Junhong; Wang, Pengchen; Chen, Guobing

doi:10.2139/ssrn.3720772

Cited by 3 publications

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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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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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“…In our previous work, we identified a couple of dominant CD8 + T cell epitopes in the Spike protein (S) of SARS-CoV-2. 20 Structural proteins of SARS-CoV-2, including S, membrane (M), nucleocapsid (N), and envelope (E) proteins, are the main targets that are recognized by the host immune system. In this study, we predicted the potential CD8 + T cell epitopes within the structural proteins of SARS-CoV-2, and analyzed the immune properties of these epitopes, including MHC I binding and activation of CD8 + T cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins

Deng

Jiang

Qiu

et al. 2021

Journal of Leukocyte Biology

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The outbreak of coronavirus disease 2019 (COVID-19) has now become a pandemic, and the etiologic agent is the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). T cell mediated immune responses play an important role in virus controlling; however, the understanding of the viral protein immunogenicity and the mechanisms of the induced responses are still limited. So, identification of specific epitopes and exploring their immunogenic properties would provide valuable information.In our study, we utilized the Immune Epitope Database and Analysis Resource and NetMHCpan to predict HLA-A2 restricted CD8 + T cell epitopes in structural proteins of SARS-CoV-2, and screened out 23 potential epitopes. Among them, 18 peptides showed strong or moderate binding with HLA-A2 with a T2A2 cell binding model. Next, the mixed peptides induced the increased expression of CD69 and highly expressed levels of IFN-γ and granzyme B in CD8 + T cells, indicating effective activation of specific CD8 + T cells. In addition, the peptide-activated CD8 + T cells showed significantly increased killing to the target cells. Furthermore, tetramer staining revealed that the activated CD8 + T cells mainly recognized seven epitopes. All together, we identified specific CD8 + T cell epitopes in SARS-CoV-2 structural proteins, which could induce the production of specific immune competent CD8 + T cells. Our work contributes to the understanding of specific immune responses and vaccine development for SARS-CoV-2. K E Y W O R D S CD8+ T cells, epitope, SARS-CoV-2, structural proteinThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…All these results showed that the T cell mediated immune responses induced by variant B.1.1.7 was decreased. Our previous work has also shown that the L>F mutations in spike protein epitope FVF L VLVPLV resulted in antigen presentation deficiency and reduced specific T cell function, indicating an immune evasion induced by viral evolution(Qiu et al, 2020). The impaired immune responses were further confirmed with the epitope specific CD8 + T cells measurement from convalescent COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

“…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). 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%

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

Xiao

Wang

et al. 2021

Preprint

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The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8+ T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8+ T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8+ T cell responses from COVID-19 convalescent patients recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8+ T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8+ T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8+ T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238. Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8+ T cell responses elicited by infection of mutated strains.

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

Cited by 3 publications

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

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

Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins

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

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

Cited by 3 publications

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

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

Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins

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

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