The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA-supertype-dependent manner

Hamelin, David; Fournelle, Dominique; Grenier, Jean; Schockaert, Jana; Kovalchik, Kevin; Kubiniok, Peter; Mostefai, Fatima; Duquette, Jérôme Despault; Saab, Frederic; Sirois, Isabelle; Smith, Martin A.; Pattijn, Sofie; Soudeyns, Hugo; Decaluwe, Hélène; Hussin, Julie; Caron, Étienne

doi:10.1016/j.cels.2021.09.013

Cited by 29 publications

(33 citation statements)

References 92 publications

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“…All analyses were conducted using R version 3.6 [ 18 ], and main packages RISmed 2.1 for queries on journal characteristics [ 19 ], easyPubMed 2.13 for queries on article characteristics [ 20 ], DescTools 0.99 for Gini index calculation [ 21 ], and tidyverse 1.3 for miscellaneous [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

A survey of biomedical journals to detect editorial bias and nepotistic behavior

et al. 2021

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Alongside the growing concerns regarding predatory journal growth, other questionable editorial practices have gained visibility recently. Among them, we explored the usefulness of the Percentage of Papers by the Most Prolific author (PPMP) and the Gini index (level of inequality in the distribution of authorship among authors) as tools to identify journals that may show favoritism in accepting articles by specific authors. We examined whether the PPMP, complemented by the Gini index, could be useful for identifying cases of potential editorial bias, using all articles in a sample of 5,468 biomedical journals indexed in the National Library of Medicine. For articles published between 2015 and 2019, the median PPMP was 2.9%, and 5% of journal exhibited a PPMP of 10.6% or more. Among the journals with the highest PPMP or Gini index values, where a few authors were responsible for a disproportionate number of publications, a random sample was manually examined, revealing that the most prolific author was part of the editorial board in 60 cases (61%). The papers by the most prolific authors were more likely to be accepted for publication within 3 weeks of their submission. Results of analysis on a subset of articles, excluding nonresearch articles, were consistent with those of the principal analysis. In most journals, publications are distributed across a large number of authors. Our results reveal a subset of journals where a few authors, often members of the editorial board, were responsible for a disproportionate number of publications. To enhance trust in their practices, journals need to be transparent about their editorial and peer review practices.

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Section: Methodsmentioning

confidence: 99%

A survey of biomedical journals to detect editorial bias and nepotistic behavior

et al. 2021

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“…Studies to date demonstrate moderate to high T cell cross-reactivity against circulating variants, including the Omicron variant, [74][75][76] with strong reactivity particularly in the CD4 + compartment. 67,70,72,[77][78][79] Indeed, T cell epitopes identified in CSTs from convalescent patients span the viral proteome 40,50,[80][81][82] and stimulate T cell responses to viral variants that are partially resistant to vaccine-induced humoral spikespecific responses. [83][84][85] Importantly, high throughput systematic analysis of CD8 + T cell activity in response to mutant peptides from SARS-CoV-2 variants of concern-including alpha, beta, and delta variants-has suggested decreased ability of some mutant epitopes to bind to certain HLA, 86,87 which highlights the need to ensure that CSTs generated for clinical use maintain activity against circulating strains as new variants arise.…”

Section: Clinical Use Of Sars-cov-2-specific T Cellsmentioning

confidence: 99%

Cellular therapies for the treatment and prevention of SARS-CoV-2 infection

Conway

Keller

Bollard

2022

Blood

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Patients with blood disorders who are immune suppressed are at increased risk for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Sequelae of infection can include severe respiratory disease and/or prolonged duration of viral shedding. Cellular therapies may protect these vulnerable patients by providing anti-viral cellular immunity and/or immune modulation. In this recent Review of the field, phase I/II trials evaluating adoptive cellular therapies with virus-specific T cells or natural killer cells are described along with trials evaluating the safety, feasibility, and preliminary efficacy of immune modulating cellular therapies including regulatory T cells and mesenchymal stromal cells. In addition, the immunological basis for these therapies is discussed.

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“…If variants of the pathogen emerge (1), some HLA allomorphs will not be able to recognize the peptides corresponding to the regions where there has been a mutation (or will bind sub-optimally to them), and this will lead to a loss of the corresponding TCR epitopes. The loss of the TCR epitope with regards to variant and specific HLA allomorphs has been described, for example, in the case of SARS-CoV-2 [ 53 , 54 , 55 ] (Reynolds et al, in Supplementary Materials ). Individuals who have lost TCR epitopes in memory T cells will have a greater chance of being reinfected.…”

Section: Hypothesesmentioning

confidence: 99%

“…In addition, the HLA allomorphs could differ depending on the variant of the virus responsible for the relapse. It can then be verified that the impact of the mutation on the peptides in their recognition by the allomorphs was predictable [ 53 , 54 , 55 ], thanks to the analyses and prediction of the peptide/HLA binding using for example NetMHCpan [ 58 ], and/or a test for TCR recognition against the variant peptide plus HLA, as described for example by Tarke et al [ 48 ] and Reynolds et al [ 55 ]. This will show that individuals with certain HLA allomorphs will be disadvantaged and will have less chance of survival compared to individuals with other allomorphs and, therefore, the frequency of the allomorphs should change.…”

Section: Testing the Hypothesesmentioning

confidence: 99%

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Pontarotti

Paganini²

2022

IJMS

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We propose a new hypothesis that explains the maintenance and evolution of MHC polymorphism. It is based on two phenomena: the constitution of the repertoire of naive T lymphocytes and the evolution of the pathogen and its impact on the immune memory of T lymphocytes. Concerning the latter, pathogen evolution will have a different impact on reinfection depending on the MHC allomorph. If a mutation occurs in a given region, in the case of MHC allotypes, which do not recognize the peptide in this region, the mutation will have no impact on the memory repertoire. In the case where the MHC allomorph binds to the ancestral peptides and not to the mutated peptide, that individual will have a higher chance of being reinfected. This difference in fitness will lead to a variation of the allele frequency in the next generation. Data from the SARS-CoV-2 pandemic already support a significant part of this hypothesis and following up on these data may enable it to be confirmed. This hypothesis could explain why some individuals after vaccination respond less well than others to variants and leads to predict the probability of reinfection after a first infection depending upon the variant and the HLA allomorph.

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The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA-supertype-dependent manner

Cited by 29 publications

References 92 publications

A survey of biomedical journals to detect editorial bias and nepotistic behavior

A survey of biomedical journals to detect editorial bias and nepotistic behavior

Cellular therapies for the treatment and prevention of SARS-CoV-2 infection

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

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