Identification of Three Novel CTL Epitopes within Nucleocapsid Protein of Hantaan Virus

Wang, Meiliang; Zhu, Yi‐Chun; Wang, Jiuping; Lv, Tianjing; Jin, Boquan

doi:10.1089/vim.2011.0026

Cited by 16 publications

(19 citation statements)

References 24 publications

(22 reference statements)

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“…NP is highly immunogenic, inducing vigorous cellular and humoral immune responses in humans, and conserved among viral species. GP is not only responsible for receptor binding and membrane fusion, but is also considered the main target of neutralizing antibodies (Wang et al, 2011). T cells are essential components of the immune response to most viral infections.…”

Section: Introductionmentioning

confidence: 99%

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

Cheng

Ying

et al. 2016

Front. Cell. Infect. Microbiol.

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The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-Kb-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-Kb. Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-Kb-restricted CTL epitope with involvement in the host immune response to HTNV infection.

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Section: Introductionmentioning

confidence: 99%

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

Cheng

Ying

et al. 2016

Front. Cell. Infect. Microbiol.

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“…Recently, we have reported three novel CTL epitopes on HTNV-NP, including aa197–aa205, aa245–aa253, and aa258–aa266, which were restricted by various HLA alleles, including A11, A24, and B7 [27]. In addition, HTNV-NP C-terminal polypeptides aa301–aa315, aa355–aa369, and aa415–aa429 could induce strong CD8 + T-cell responses [28].…”

Section: Introductionmentioning

confidence: 99%

HLA-A2 and B35 Restricted Hantaan Virus Nucleoprotein CD8+ T-Cell Epitope-Specific Immune Response Correlates with Milder Disease in Hemorrhagic Fever with Renal Syndrome

Wang

Yuan

et al. 2013

PLoS Negl Trop Dis

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BackgroundHantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored.Methodology/Principal FindingsFive well-conserved novel CD8+ T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129–aa137 and aa131–aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8+ T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8+ T cell could be detected in patients (95% confidence interval for aa129–aa137: 0.080%–0.208%; for aa131–aa139: 0.030%–0.094%). The frequency of epitope-specific pentamer+ CD8+ T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8+ T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8+ T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation.Conclusion/SignificanceThe novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8+ T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans.

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“…To assess HTNV-specific responses, HTNV NP 9-mer peptide pools were used to stimulate the PBMCs of HFRS patients in vitro during the early phase. The peptide pools contained 14 peptides that were confirmed to be HTNV NP CTL epitopes in our previous study (14)(15)(16). Detailed information regarding the 14 epitopes can be found in Table 1.…”

Section: Methodsmentioning

confidence: 99%

CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

Liu

Yusi

et al. 2015

J Virol

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Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8؉ T cells play a critical role in combating HTNV infections. However, the contributions of different CD8 ؉ T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8 CD8 T cells play a critical role in combating viral infections. Dramatic cellular changes occur as T cells transition through the following three characteristic phases of an antiviral response: initial activation and expansion, the death phase, and the formation of memory T cells. However, many aspects of these activation and differentiation processes are inadequately understood, particularly in humans. There are several important cell surface molecules that regulate the interactions between immune cells and, moreover, characterize cell differentiation and activation status.Sema4D, also called CD100, was the first immune semaphorin discovered (1) and is involved in several aspects of both humoral and cellular immunity (2-6). CD100 exists in both a membranebound form and a soluble form. Membrane-associated CD100 is expressed preferentially on T cells and weakly on B cells and antigen-presenting cells (APCs) (2, 7). CD72, the receptor for CD100, is expressed primarily on immune system cells and is present on the surface of most APCs and B cells. Interaction between CD72 and CD100 leads to dendritic cell (DC) maturation and cytokine production and enhances B cell activation (7).Because of the involvement of CD100 in the immune response, we hypothesized that CD100 may play an important role in the antiviral CD8 T cell response. However, there is limited information available regarding the role of CD100 in infectious diseases. Eriksson et al. (8) investigated the effects of HIV-1 infection on CD100 expression in T cells, and they observed that a subset of CD8 ϩ T cells lacking membrane-associated CD100 showed decreased functional capacity. Their findings suggested that loss of CD100 expression would most likely lead to dysfunctional immunity in HIV-1 infection. It is well accepted that there are many differences between acute infections and chronic infections. Acute infections usually result in effective antiviral immune responses, while chronic infections are often associated with suboptimal T cell function. Furthermore, HIV infects CD4 ϩ T cells and B cells and has profound pathological effects on the immune system, further confounding the interpretation of T cell dynamics following the acute phase. Therefore, it is important to investigate the functional role of CD100 in the CD8 antiviral response in acute infections.

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Identification of Three Novel CTL Epitopes within Nucleocapsid Protein of Hantaan Virus

Cited by 16 publications

References 24 publications

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

HLA-A2 and B35 Restricted Hantaan Virus Nucleoprotein CD8+ T-Cell Epitope-Specific Immune Response Correlates with Milder Disease in Hemorrhagic Fever with Renal Syndrome

CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

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Identification of Three Novel CTL Epitopes within Nucleocapsid Protein of Hantaan Virus

Cited by 16 publications

References 24 publications

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus

HLA-A2 and B35 Restricted Hantaan Virus Nucleoprotein CD8+ T-Cell Epitope-Specific Immune Response Correlates with Milder Disease in Hemorrhagic Fever with Renal Syndrome

CD8lowCD100−T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

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CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection