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Impaired Priming of SARS-CoV-2-Specific Naive CD8⁺ T Cells in Older Subjects.

ABSTRACT: Advanced age is associated with severe symptoms and death upon SARS-CoV-2 infection. Virus-specific CD8⁺ T-cell responses have shown to be protective toward critical COVID-19 manifestations, suggesting that suboptimal cellular immunity may contribute to the age-pattern of the disease. The induction of a CD8⁺ T-cell response against an emerging pathogen like SARS-CoV-2 relies on the activation of naive T cells. To investigate whether the primary CD8⁺ T-cell response against this virus is defective in advanced age, we used an in vitro approach to prime SARS-CoV-2-specific naive CD8⁺ T cells from healthy, unexposed donors of different age groups. Compared to younger adults, older individuals display a poor SARS-CoV-2-specific T-cell priming capacity in terms of both magnitude and quality of the response. In addition, older subjects recognize a lower number of epitopes. Our results implicate that immune aging is associated with altered primary SARS-CoV-2-specific CD8⁺ T-cell responses.

SUBMITTER: Gallerani E

PROVIDER: S-EPMC8315546 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8+ T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population.MethodsWe selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8+ T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8+ T cell-specific response was monitored. The conserved peptide-specific CD8+ T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort.ResultsFor each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8+ T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population.ConclusionsThis study provides evidence of broad-spectrum SARS-CoV-2 specific CD8+ TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19.

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Impaired Priming of SARS-CoV-2-Specific Naive CD8⁺ T Cells in Older Subjects.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Impaired Priming of SARS-CoV-2-Specific Naive CD8+ T Cells in Older Subjects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Impaired Priming of SARS-CoV-2-Specific Naive CD8⁺ T Cells in Older Subjects.