Human T-cell immunity against the emerging and re-emerging viruses

Zhao, Min; Zhang, Hangjie; Liu, Kefang; Gao, George F.; Liu, William J.

doi:10.1007/s11427-017-9241-3

Cited by 25 publications

(15 citation statements)

References 93 publications

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“…Common respiratory viruses include CoV, influenza A virus (IAV), influenza B virus, respiratory syncytial virus, parainfluenza virus, adenovirus, etc. CoV belongs to the virus family Coronaviridae , which is an enveloped, nonsegmented, single-stranded positive-sense RNA virus ( Zhao et al., 2017 ). SARS-CoV-2 is a β-coronavirus, like Middle East respiratory syndrome (MERS)-CoV and SARS-CoV, both of which are also suggested to have originated in bats ( Zhou et al., 2020b ).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

et al. 2020

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The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin ( IL ) 6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

et al. 2020

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“…Cellular immunity plays a key role in the control of influenza virus infection ( 9 – 13 ). CD4 + T cells can promote effective immunity by providing secondary signals for antibody (Ab) responses and produce cytokines upon infection ( 14 ), while cytotoxic CD8 + T cells can provide partial protection and reduce symptoms by promoting viral clearance ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses

Zhao

Liu

Luo

et al. 2018

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Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

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“…Cross-reactive CD8 + T cells broadly exist among the population and play a pivotal role in the defense against viral infections. A number of cross-presented T-cell epitopes have been identified thus far (32,(62)(63)(64). Most of these are cross-recognized by the same HLA supertype because they have similar binding motifs.…”

Section: Discussionmentioning

confidence: 99%

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides

et al. 2019

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Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A * 30:01 and -A * 30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A * 30:01 and -A * 30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A * 30:01, and -A * 30:03 were similar to those of HLA-A * 11:01 in the A3 supertype. However, HLA-A * 30:03, but not -A * 30:01, also showed binding with the HLA * 01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A * 30:01 and -A * 30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A * 30:01 and -A * 30:03. Interchanging residue 77 between HLA-A * 30:01 and HLA-A * 30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.

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Human T-cell immunity against the emerging and re-emerging viruses

Cited by 25 publications

References 93 publications

Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides

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