☆ 4.5 Review

A systemic review of T-cell epitopes defined from the proteome of SARS-CoV-2

VIRUS RESEARCH (2023)

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Eunok Lee et al.

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Christopher Szeto et al.

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SARS-CoV-2 specific CD8+ T cell responses in convalescent COVID-19 individuals

Hassen Kared et al.

Summary: Characterization of T cell responses in convalescent individuals from SARS-CoV-2 infection revealed unique phenotypes and a coordinated immune response, with specific CD8(+) T cell responses directed against various epitopes from the virus proteome. The differentiation of T cells into stem cell and transitional memory subsets may be crucial for developing lasting protection against the virus.

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Nina Le Bert et al.

Summary: The efficacy of virus-specific T cells in clearing pathogens involves a delicate balance between antiviral and inflammatory responses. Asymptomatic individuals clearing SARS-CoV-2 showed increased production of IFN-gamma and IL-2, along with a proportional secretion of IL-10 and proinflammatory cytokines, while symptomatic individuals displayed a disproportionate secretion of inflammatory cytokines triggered by SARS-CoV-2-specific T cell activation.

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Ke Pan et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection

Jianmin Zuo et al.

Summary: The study shows that functional SARS-CoV-2-specific T cell responses are retained and robust at 6 months following infection, with higher T cell responses observed in donors who had experienced symptomatic infection. Levels of nucleoprotein-specific T cells were correlated with nucleoprotein-specific antibody levels, providing insights into the persistence and correlation of immune responses.

NATURE IMMUNOLOGY (2021)

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Assessment of SARS-CoV-2 specific CD4(+) and CD8 (+) T cell responses using MHC class I and II tetramers

Yuri Poluektov et al.

Summary: The study focuses on evaluating the binding affinities of SARS-CoV-2 peptides to different MHC alleles using the QuickSwitchTM platform, identifying multiple MHC binders with high promiscuity. These results provide important data for further research on the SARS-CoV-2 virus and its antigenic epitopes.

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SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

Juan Zhao et al.

Summary: Research shows that COVID-19-recovered individuals exhibit specific T cell responses, potentially offering protection against reinfection for some exposed individuals and inducing protective immunity in unexposed individuals upon vaccination. There is a need for a multi-epitope strategy in COVID-19 vaccine design due to the low immunogenicity of SARS-CoV-2 S and N peptides at inducing robust T cell responses.

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SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses

Benedikt Agerer et al.

Summary: The study identified nonsynonymous mutations in MHC-I-restricted CD8(+) T cell epitopes of SARS-CoV-2 virus isolates, which resulted in diminished MHC-I binding of mutant peptides. This led to decreased proliferation, IFN-gamma production, and cytotoxic activity of CD8(+) T cells, along with qualitative differences in the transcriptional response to mutant peptides. These findings highlight the ability of SARS-CoV-2 to evade CD8(+) T cell surveillance through point mutations in MHC-I-restricted viral epitopes.

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Cross-reactive and mono-reactive SARS-CoV-2 CD4+T cells in prepandemic and COVID-19 convalescent individuals

Alexandra M. Johansson et al.

Summary: This study identified SARS-CoV-2 CD4+ T cell epitopes using tetramer reagents, distinguishing immunodominant and subdominant epitopes. Among the four potential Spike-specific cross-reactive epitopes identified, three were subdominant epitopes, while only one was an immunodominant epitope.

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Peptides Derived From S and N Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Induce T Cell Responses: A Proof of Concept for T Cell Vaccines

Yu-Sun Lee et al.

Summary: This study demonstrates the importance of T cell responses against SARS-CoV-2 and the potential of peptide vaccines to induce protective immune responses. Immunization with these peptides increases effector memory T cells and IFN-gamma, IL-4, TNF-alpha, and granzyme B-producing T cells, while some peptides induce IFN-gamma-producing T cells and CTL responses, leading to cytotoxic T lymphocytes that eliminate target cells. Peptide vaccines also show promise in reducing viral titers and alleviating pulmonary pathology in animal models of SARS-CoV-2 infection.

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CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses

Katie E. Lineburg et al.

Summary: Efforts are being made to understand the immune response to SARS-CoV-2, with a focus on T cell immunity and cross-recognition with seasonal coronaviruses. Research has shown that the N protein of SARS-CoV-2 induces an immunodominant response and T cells demonstrate cross-reactivity towards certain coronaviruses through specific peptide conformations.

IMMUNITY (2021)

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Immunogenic T cell epitopes of SARS-CoV-2 are recognized by circulating memory and naive CD8 T cells of unexposed individuals

Isaac Quiros-Fernandez et al.

Summary: Recent studies have shown evidence of cross-reactive CD8 T cells in non-exposed individuals to SARS-CoV-2, which can stabilize HLA molecules and activate CD8 T cells in healthy unexposed subjects. The reactive cells were found in naive, memory, and effector subsets, indicating a diverse T cell response in individuals without previous exposure to the virus.

EBIOMEDICINE (2021)

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Article Immunology

Genome-Wide B Cell, CD4+, and CD8+ T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines

Swayam Prakash et al.

Summary: The study identified several conserved human B cell and T cell epitopes across different coronaviruses, suggesting potential for developing a pan-coronavirus vaccine; these epitopes triggered immune responses in both COVID-19 patients and individuals never exposed to SARS-CoV-2, as well as in double-transgenic mice; paving the way for a preemptive multiepitope pancoronavirus vaccine to protect against past, current, and future outbreaks.

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Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2

Kanako Shimizu et al.

Summary: Identification of immunodominant epitopes in the SARS-CoV-2 spike region provides insight into cross-reactivity of CD8(+) T cells. Cross-reactive CD8(+) T cells are reduced in immunosuppressed patients with hematological malignancy. T-cell receptors isolated from selective pre-existing CD8(+) T cells exhibit diverse cross-reactivity at the single-cell level.

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Article Multidisciplinary Sciences

Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2

Jun Siong Low et al.

Summary: The study demonstrates a robust CD4(+) T cell response to SARS-CoV-2 spike and nucleoprotein in COVID-19-recovered individuals, with a highly immunogenic receptor-binding domain (RBD). Through characterizing T cell clones, it was found that a region containing nested HLA-DR and HLA-DP-restricted epitopes is immunodominant. Cross-reactive T cells targeting multiple S protein sites were identified, which can guide vaccination strategies against emerging SARS-CoV-2 variants.

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Identification and characterization of a SARS-CoV-2 specific CD8+ T cell response with immunodominant features

Anastasia Gangaev et al.

Summary: This study identified a range of SARS-CoV-2 CD8(+) T cell responses across COVID-19 patients, including an epitope from ORF1ab with immunodominant features. The specific CD8(+) T cell responses can still be detectable up to 5 months after recovery from critical and severe disease, converting from dysfunctional effector cells to functional memory cells during convalescence.

NATURE COMMUNICATIONS (2021)

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SARS-CoV-2-Seronegative Subjects Target CTL Epitopes in the SARS-CoV-2 Nucleoprotein Cross-Reactive to Common Cold Coronaviruses

Katja G. Schmidt et al.

Summary: Research suggests that cross-reactive T-cell responses to SARS-CoV-2 may influence the severity of infection in certain populations. In HIV-1 patients, approximately 37.9% showed T-cell reactivity to SARS-CoV-2, potentially impacting the development of severe COVID-19.

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Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation

Lauren M. Meyers et al.

Summary: This study identified peptide epitopes associated with SARS-CoV-2 T-cell immunity and demonstrated epitope-specific T-cell responses through direct restimulation and T-cell expansion. Immunization of HLA-DR3 transgenic mice generated a potent Th1-skewed, epitope-specific memory response, offering a potential approach for developing T-cell-targeted vaccines.

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SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients

Sunil Kumar Saini et al.

Summary: This study experimentally evaluated MHC class I-binding peptides covering the complete SARS-CoV-2 genome, revealing significant CD8(+) T cell recognition of SARS-CoV-2 epitopes in patients with COVID-19, coupled with strong activation features in these T cells. Compared to healthy individuals, patients with severe disease displayed larger populations of SARS-CoV-2-specific T cells.

SCIENCE IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

Shira Weingarten-Gabbay et al.

Summary: T cell-mediated immunity plays a crucial role in controlling SARS-CoV-2 infection, with some peptides derived from internal out-of-frame ORFs in spike and nucleocapsid eliciting stronger T cell responses than canonical peptides. Early expressed viral proteins contribute more to HLA-I presentation and immunogenicity, providing insights for vaccine development and immune monitoring.

CELL (2021)

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Article Immunology

Human CD4+ T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential

Johan Verhagen et al.

Summary: Since December 2019, the rapid spread of COVID-19 has prompted a global effort to develop vaccines and treatments. T cell therapy may enhance the efficacy of current treatments by targeting specific antigens of the virus. Identifying T cells with potentially protective responses against key SARS-CoV-2 antigens is a crucial step towards TCR-transgenic CD4(+) T cell therapy for COVID-19.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY (2021)

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SARS-CoV-2-specific CD8+ T-cell responses and TCR signatures in the context of a prominent HLA-A*24:02 allomorph

Louise C. Rowntree et al.

Summary: This study identified novel HLA-A*24:02-restricted epitopes of SARS-CoV-2 and characterized the CD8(+) T-cell responses associated with this HLA allomorph during COVID-19. The frequencies of A24/SARS-CoV-2-specific CD8(+) T cells increased substantially during COVID-19, showing effector and memory phenotypes. Ex vivo analyses of TCR alpha beta repertoires revealed distinct differences in repertoire diversity among COVID-19 patients for different epitopes.

IMMUNOLOGY AND CELL BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Structural basis of biased T cell receptor recognition of an immunodominant HLA-A2 epitope of the SARS-CoV-2 spike protein

Priyanka Chaurasia et al.

Summary: CD8(+) T cells are crucial in immunity against SARS-CoV-2 infection, with the HLA-A2S(269-277) epitope being the most immunodominant. Studies show that TRAV12(+) T cell receptors are sensitive to sequence variation within the S269-277 peptide. However, the TRAV12(+) T cell repertoire demonstrates poor cross-reactivity with analogous epitopes from SARS-CoV-2 variants and related coronaviruses.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Article Immunology

Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019

Yipeng Ma et al.

Summary: The study identified 7 epitopes derived from 4 SARS-CoV-2 proteins, with most peptides being HLA-II-restricted and inducing CD4 + T cell-dependent responses. These findings suggest the presence of pre-existing T cells targeting all SARS-CoV-2-encoded proteins in unexposed populations.

JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Cell Biology

Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins

Jieping Deng et al.

Summary: This study identified specific CD8(+) T cell epitopes in the structural proteins of SARS-CoV-2, which effectively activated and induced the production of specific immune competent CD8(+) T cells by predicting specific epitopes and exploring their immunogenic properties.

JOURNAL OF LEUKOCYTE BIOLOGY (2021)

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Article Multidisciplinary Sciences

Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine

Valerie Oberhardt et al.

Summary: After vaccination, CD8(+) T cells become important effector cells in providing early protection, being effectively mobilized one week after primary vaccination and maintaining stability after booster vaccination. Compared with natural infection, vaccine-induced CD8(+) T cells exhibit similar functional capacities but with a different subset distribution.

NATURE (2021)

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Article Multidisciplinary Sciences

Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

Lucie Loyal et al.

Summary: The study demonstrates that preexisting spike-cross-reactive T cells play a functional role in the immune response to SARS-CoV-2 infection and vaccination. Cross-reactive immunity may explain the rapid induction of immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic or mild COVID-19 cases.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals

Swapnil Mahajan et al.

Summary: The study identified immunodominant CD8 T-cell epitopes in the spike antigen of SARS-CoV-2, which induced robust T-cell activation in unexposed donors. Pre-existing T-cell immunity to SARS-CoV-2 is likely contributed by TCRs recognizing common viral antigens such as Influenza and CMV rather than shared epitopes with other coronaviruses.

SCIENTIFIC REPORTS (2021)

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Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics

Adi Nagler et al.

Summary: This study identified SARS-CoV-2-derived peptides presented by HLA-I and HLA-II molecules, some of which are immunogenic, potentially aiding in the development of next-generation SARS-CoV-2 vaccines.

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Profiling CD8+ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants

Hang Zhang et al.

Summary: Cellular immunity plays a crucial role in determining the disease severity of COVID-19 patients. Identified epitopes from SARS-CoV-2 are conserved across human coronaviruses, suggesting a potential pre-existing cellular immunity. Mutations in newly circulating variants reduce T cell responses to epitopes, indicating a possible evasion of cellular immunity.

CELL REPORTS (2021)

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Article Microbiology

Broadly directed SARS-CoV-2-specific CD4+T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19

Janna Heide et al.

Summary: The study aimed to explore the CD4+ T cell response to SARS-CoV-2 and found a universally broad T cell response in patients, identifying multiple specific peptides. These findings are important for understanding the immunopathogenesis of SARS-CoV-2 infection and vaccine design.

PLOS PATHOGENS (2021)

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Article Immunology

BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity

Peter J. Eggenhuizen et al.

Summary: The Bacillus Calmette-Guerin (BCG) vaccine can enhance T cell response to the SARS-CoV-2 virus, providing a potential mechanism for the observed protective effects against COVID-19.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Genetics & Heredity

A Peptide Vaccine Candidate Tailored to Individuals' Genetics Mimics the Multi-Targeted T Cell Immunity of COVID-19 Convalescent Subjects

Eszter Somogyi et al.

Summary: Long-term immunity to coronaviruses is likely T cell-based. A novel approach was presented to select immunoprevalent SARS-CoV-2 T cell epitopes, leading to the development of a peptide vaccine candidate. Results showed robust multi-antigenic T cell responses induced by PolyPEPI-SCoV-2 vaccination, suggesting its potential as a highly immunogenic global vaccine.

FRONTIERS IN GENETICS (2021)

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Article Medicine, Research & Experimental

SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63

Bezawit A. Woldemeskel et al.

Summary: Recent studies have shown that T cells can cross-recognize spike proteins of SARS-CoV-2 and common cold coronaviruses. Vaccination with SARS-CoV-2 mRNA vaccines results in broad T cell responses to the virus's spike protein, including potential recognition of variant spike proteins. Additionally, post-vaccination, there is an observed increase in CD4(+) T cell responses to certain common cold coronaviruses.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Medicine, Research & Experimental

Functional characterization of CD4+ T cell receptors crossreactive for SARS-CoV-2 and endemic coronaviruses

Arbor G. Dykema et al.

Summary: Our study confirms the presence of unique memory CD4(+) T cell clones recognizing both SARS-CoV-2 and CCCs. The lower avidity of crossreactive TCRs for SARS-CoV-2 may result in reduced proliferation capacity and impact clinical outcomes in COVID-19 patients. Further research is needed to fully understand the implications of these crossreactive T cell responses.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Virology

Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle

Yingying Cong et al.

JOURNAL OF VIROLOGY (2020)

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Article Cell Biology

Insights into the polymorphism in HLA-DRA and its evolutionary relationship with HLA haplotypes

Ben M. Matern et al.

HLA (2020)

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Article Biochemistry & Molecular Biology

Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

Alba Grifoni et al.

CELL (2020)

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Article Microbiology

Regulation of the ER Stress Response by the Ion Channel Activity of the Infectious Bronchitis Coronavirus Envelope Protein Modulates Virion Release, Apoptosis, Viral Fitness, and Pathogenesis

Shumin Li et al.

FRONTIERS IN MICROBIOLOGY (2020)

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Article Biochemical Research Methods

Benchmarking predictions of MHC class I restricted T cell epitopes in a comprehensively studied model system

Sinu Paul et al.

PLoS Computational Biology (2020)

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Article Multidisciplinary Sciences

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Jun Lan et al.

NATURE (2020)

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Review Pharmacology & Pharmacy

Coronavirus membrane fusion mechanism offers a potential target for antiviral development

Tiffany Tang et al.

ANTIVIRAL RESEARCH (2020)

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Letter Hematology

Harnessing HLA-E-restricted CD8 T lymphocytes for adoptive cell therapy of patients with severe COVID-19

Nadia Caccamo et al.

BRITISH JOURNAL OF HAEMATOLOGY (2020)

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Review Biochemistry & Molecular Biology

Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach

Ahmad Abu Turab Naqvi et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2020)

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Article Biochemistry & Molecular Biology

Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

Takuya Sekine et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Carolyn Rydyznski Moderbacher et al.

CELL (2020)

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Article Multidisciplinary Sciences

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls

Nina Le Bert et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

Jose Mateus et al.

SCIENCE (2020)

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Article Genetics & Heredity

Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes

Asaf Poran et al.

GENOME MEDICINE (2020)

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Article Immunology

Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein

Andrew P. Ferretti et al.

IMMUNITY (2020)

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Article Immunology

Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

Yanchun Peng et al.

NATURE IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype

Jennifer R. Habel et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Hematology

SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein

Michael D. Keller et al.

BLOOD (2020)

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Article Immunology

Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience

Roberto Littera et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Cell Biology

Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility

Fang Wang et al.

CELL DISCOVERY (2020)

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Article Biochemistry & Molecular Biology

Age-related rhesus macaque models of COVID-19

Pin Yu et al.

ANIMAL MODELS AND EXPERIMENTAL MEDICINE (2020)

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Article Gastroenterology & Hepatology

Hepatitis B virus infection and the immune response: The big questions

Lauke L. Boeijen et al.

BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY (2017)

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Article Gastroenterology & Hepatology

CD8+T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Katja Nitschke et al.

DIGESTIVE DISEASES (2016)

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Review Immunology

Clinical Relevance of HLA Gene Variants in HBV Infection

Li Wang et al.

JOURNAL OF IMMUNOLOGY RESEARCH (2016)

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Article Cell Biology

HLA-E polymorphism and soluble HLA-E plasma levels in chronic hepatitis B patients

I. Zidi et al.

HLA (2016)

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Review Immunology

The ins and outs of MHC class II-mediated antigen processing and presentation

Paul A. Roche et al.

NATURE REVIEWS IMMUNOLOGY (2015)

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Article Biochemical Research Methods

Intracellular cytokine detection by fluorescence-activated flow cytometry: Basic principles and recent advances

Giulia Freer et al.

METHODS (2013)

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Article Biochemistry & Molecular Biology

Association of HLA-alleles with the immune regulation of chronic viral infections

Shokrollah Elahi et al.

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY (2012)

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Review Multidisciplinary Sciences

Recognition of microorganisms and activation of the immune response

Ruslan Medzhitov

NATURE (2007)

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