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The presentation of SARS-CoV-2 peptides by the common HLA-A^∗02:01 molecule.

ABSTRACT: CD8+ T cells are crucial for anti-viral immunity; however, understanding T cell responses requires the identification of epitopes presented by human leukocyte antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins are typically more conserved than surface proteins and are often the target of CD8+ T cells. Therefore, we have characterized eight peptides derived from the internal SARS-CoV-2 nucleocapsid protein predicted to bind HLA-A^∗02:01, the most common HLA molecule in the global population. We determined not all peptides could form a complex with HLA-A^∗02:01, and the six crystal structures determined revealed that some peptides adopted a mobile conformation. We therefore provide a molecular understanding of SARS-CoV-2 CD8+ T cell epitopes. Furthermore, we show that there is limited pre-existing CD8+ T cell response toward these epitopes in unexposed individuals. Together, these data show that SARS-CoV-2 nucleocapsid might not contain potent epitopes restricted to HLA-A^∗02:01.

SUBMITTER: Szeto C

PROVIDER: S-EPMC7825995 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The presentation of SARS-CoV-2 peptides by the common HLA-A<sup>∗</sup>02:01 molecule.

Szeto Christopher C Chatzileontiadou Demetra S M DSM Nguyen Andrea T AT Sloane Hannah H Lobos Christian A CA Jayasinghe Dhilshan D Halim Hanim H Smith Corey C Riboldi-Tunnicliffe Alan A Grant Emma J EJ Gras Stephanie S

iScience 20210122 2

CD8+ T cells are crucial for anti-viral immunity; however, understanding T cell responses requires the identification of epitopes presented by human leukocyte antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins are typically more conserved than surface proteins and are often the target of CD8+ T cells. Therefore, we have characterized eight peptides derived from the internal SARS-CoV-2 nucleocapsid protein predicted to bind HLA-A<sup ...[more]

PMID: 33521593

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction model for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February-August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27-3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24-3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50-7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01-1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31-6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A*11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article that describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

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The presentation of SARS-CoV-2 peptides by the common HLA-A^∗02:01 molecule.

Publications

The presentation of SARS-CoV-2 peptides by the common HLA-A<sup>∗</sup>02:01 molecule.

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Dataset Information

The presentation of SARS-CoV-2 peptides by the common HLA-A∗02:01 molecule.

Publications

The presentation of SARS-CoV-2 peptides by the common HLA-A<sup>∗</sup>02:01 molecule.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The presentation of SARS-CoV-2 peptides by the common HLA-A^∗02:01 molecule.