Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2

Wilson, Eric; Hirneise, Gabrielle; Singharoy, Abhishek; Anderson, Karen S.

doi:10.1101/2020.05.08.20095430

Cited by 11 publications

(9 citation statements)

References 47 publications

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“…CTLs recognize the nonself epitopes that are presented on virus-infected cells via human leukocyte antigen (HLA) class I molecules, and therefore, the CTL-mediated antiviral immunity is HLA-restricted [reviewed in (La Gruta et al, 2018)]. Recent studies have reported the HLA-restricted SARS-CoV-2-derived epitopes that can be recognized by human CTLs (Kared et al, 2021;Kiyotani et al, 2020;Nelde et al, 2021;Schulien et al, 2021;Wilson et al, 2021). More importantly, Bert et al have recently reported that the functionality of virus-specific cellular immunity is inversely correlated to the COVID-19 severity (Le Bert et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity

Motozono

Toyoda

Zahradník

et al. 2021

Preprint

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During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, that to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here we demonstrate that two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. These mutations reinforce the affinity to viral receptor ACE2, and notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic.

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Section: Introductionmentioning

confidence: 99%

An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity

Motozono

Toyoda

Zahradník

et al. 2021

Preprint

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“…This concern stems from the fact that the durability and potency of SARS-CoV-2 vaccines is indeed partially dictated by elicited T cell immune responses. Not examining the CoV-2 T cell immunomonitoring may result in vaccines that induce short lasting humoral responses in the absence of proper T cell memory responses [15][16][17][18][19][20]. Other than healthy hosts, it is also important to analyze CoV-2-specific T cell responses in certain vaccinated sub-populations such as the elderly, and hosts who bear underlying conditions that are expected to impact the immune system such as diabetes.…”

Section: Discussionmentioning

confidence: 99%

Assessment of SARS-CoV-2 Specific CD4(+) and CD8 (+) T Cell Responses Using MHC Class I and II Tetramers

Poluektov¹,

Daftarian

Delcommenne³

2020

Preprint

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AbstractThe success of SARS-CoV-2 (CoV-2) vaccines is measured by their ability to mount immune memory responses that are long-lasting. To achieve this goal, it is important to identify surrogates of immune protection, namely, CoV-2 MHC Class I and II immunodominant pieces/epitopes and methodologies to measure them. Here, we present results of flow cytometry-based MHC Class I and II QuickSwitch™ platforms for assessing SARS-CoV-2 peptide binding affinities to various human alleles as well as the H-2 Kb mouse allele. Multiple SARS-CoV-2 potential MHC binders were screened and validated by QuickSwitch testing. While several predicted peptides with acceptable theoretical Kd showed poor MHC occupancies, fourteen MHC class II and a few MHC class I peptides showed promiscuity in that they bind with multiple MHC molecule types. With the peptide exchange generated MHC tetramers, scientists can assess CD4+ and CD8+ immune responses to these different MHC/peptide complexes. Results obtained with several SARS-CoV-2 MHC class I and II peptides are included and discussed.

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“…13 The correlation between MHC-I and the severity of the disease in patients with COVID-19 has been previously hypothesised. 14 The understanding of which SARS-CoV-2 epitopes are immunogenic may help advances in the development of diagnostic kits and prophylactic vaccines. An immunoinformatic approach is suitable for an initial screening, since it may predict algorithms and test for the immunogenicity of a vast quantity of peptides and alleles in a cost-effective manner, reducing the costs and time on workbench.…”

Section: Original Researchmentioning

confidence: 99%

“… 13 The correlation between MHC-I and the severity of the disease in patients with COVID-19 has been previously hypothesised. 14 …”

Section: Introductionmentioning

confidence: 99%

Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population

et al. 2020

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AimsBrazil is nowadays one of the epicentres of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and new therapies are needed to face it. In the context of specific immune response against the virus, a correlation between Major Histocompatibility Complex Class I (MHC-I) and the severity of the disease in patients with COVID-19 has been suggested. Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods.MethodsOur analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes.ResultsWe identified 24 immunogenic epitopes in the SARS-CoV-2 protein S that could interact with 17 different MHC-I alleles (namely, HLA-A*01:01; HLA-A*02:01; HLA-A*11:01; HLA-A*24:02; HLA-A*68:01; HLA-A*23:01; HLA-A*26:01; HLA-A*30:02; HLA-A*31:01; HLA-B*07:02; HLA-B*51:01; HLA-B*35:01; HLA-B*44:02; HLA-B*35:03; HLA-C*05:01; HLA-C*07:01 and HLA-C*15:02) in the Brazilian population.ConclusionsBeing aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2.

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Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2

Cited by 11 publications

References 47 publications

An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity

An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity

Assessment of SARS-CoV-2 Specific CD4(+) and CD8 (+) T Cell Responses Using MHC Class I and II Tetramers

Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population

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