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CD8⁺ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

ABSTRACT: A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a "memory" phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8⁺ T cells with these conserved specificities are much more abundant in COVID-19 patients with mild disease versus those with a more severe illness, suggesting a protective role.

SUBMITTER: Mallajosyula V

PROVIDER: S-EPMC8975171 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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CD8<sup>+</sup> T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

Mallajosyula Vamsee V Ganjavi Conner C Chakraborty Saborni S McSween Alana M AM Pavlovitch-Bedzyk Ana Jimena AJ Wilhelmy Julie J Nau Allison A Manohar Monali M Nadeau Kari C KC Davis Mark M MM

Science immunology 20210701 61

A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing t ...[more]

PMID: 34210785

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Project description:BackgroundDevelopment of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protection against HIV-1 acquisition although the vaccines induced HIV-1-specific T-cell responses, suggesting that the vaccine-induced T cells have insufficient capacities to suppress HIV-1 replication and/or cross-recognize circulating HIV-1. Therefore, it is necessary to develop T-cell vaccines that elicit T cells recognizing shared protective epitopes with strong ability to suppress HIV-1. We recently designed T-cell mosaic vaccine immunogens tHIVconsvX composed of 6 conserved Gag and Pol regions and demonstrated that the T-cell responses to peptides derived from the vaccine immunogens were significantly associated with lower plasma viral load (pVL) and higher CD4+ T-cell count (CD4 count) in HIV-1-infected, treatment-naive Japanese individuals. However, it remains unknown T cells of which specificities have the ability to suppress HIV-1 replication. In the present study, we sought to identify more T cells specific for protective Gag epitopes in the vaccine immunogens, and analyze their abilities to suppress HIV-1 replication and recognize epitope variants in circulating HIV-1.ResultsWe determined 17 optimal Gag epitopes and their HLA restriction, and found that T-cell responses to 9 were associated significantly with lower pVL and/or higher CD4 count. T-cells recognizing 5 of these Gag peptides remained associated with good clinical outcome in 221 HIV-1-infected individuals even when comparing responders and non-responders with the same restricting HLA alleles. Although it was known previously that T cells specific for 3 of these protective epitopes had strong abilities to suppress HIV-1 replication in vivo, here we demonstrated equivalent abilities for the 2 novel epitopes. Furthermore, T cells against all 5 Gag epitopes cross-recognized variants in majority of circulating HIV-1.ConclusionsWe demonstrated that T cells specific for 5 Gag conserved epitopes in the tHIVconsvX have ability to suppress replication of circulating HIV-1 in HIV-1-infected individuals. Therefore, the tHIVconsvX vaccines have the right specificity to contribute to prevention of HIV-1 infection and eradication of latently infected cells following HIV-1 reactivation.

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CD8⁺ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

Publications

CD8<sup>+</sup> T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

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CD8+ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

Publications

CD8<sup>+</sup> T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.

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OmicsDI is part of the ELIXIR infrastructure

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CD8⁺ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.