HLA-A∗0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

Tsao, Yeou‐Ping; Lin, Jianyu; Jan, Jia-Tsrong; Leng, Chih‐Hsiang; Chu, Chen‐Chung; Yang, Yuh‐Cheng; Chen, Show‐Li

doi:10.1016/j.bbrc.2006.03.152

Cited by 57 publications

(68 citation statements)

References 38 publications

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“…This assay measures the increase of HLA-A*0201 molecules on the surface of T 2 cells, which is normally at a low level (44,45). Each gD peptide was tested at a concentration of 60 M (not shown) and then titrated in serial 2-fold dilution steps (Fig.…”

Section: High-affinity Gd Peptides Stabilized Hla-a*0201 Molecules Onmentioning

confidence: 99%

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

Chentoufi

Zhang

Lamberth³

et al. 2008

The Journal of Immunology

140

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Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10 amino acids in length, exhibited high-affinity binding in vitro to purified human HLA-A*0201 molecules. Three of these four peptide epitopes, gD53–61, gD70–78, and gD278–286, significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-γ ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53–61, gD70–78, and gD278–286 epitopes. In addition, CD8+ T cell lines generated by gD53–61, gD70–78, and gD278–286 peptides recognized infected target cells expressing native gD. Lastly, CD8+ T cell responses specific to gD53–61, gD70–78, and gD278–286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.

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Section: High-affinity Gd Peptides Stabilized Hla-a*0201 Molecules Onmentioning

confidence: 99%

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

Chentoufi

Zhang

Lamberth³

et al. 2008

The Journal of Immunology

140

View full text Add to dashboard Cite

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“…Subunit vaccines containing HLA-A*0201 restricted peptides is highly effective for the induction of strong cytotoxic T-cell response against infectious virus [6]. Among the four structure proteins of the SARS-CoV, the S and N proteins are the major targets for vaccine research studies due to their potency in triggering immune responses [7][8][9][10][11][12][13][14]. The S protein contains 1256 amino acids and is involved in viral entry through angiotensin-converting enzyme 2 receptor on host cell surface [15,16] and the N protein contains 422 amino acids and is involved in the viral RNA packaging [17,18].…”

Section: Introductionmentioning

confidence: 99%

Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope

Cheung

Cheng

Sin

et al. 2007

Vaccine

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The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. In this study, we have identified a novel HLA-A*0201 restricted epitope, N220 (LALLLLDRL), of the SARS-CoV N-protein through bioinformatics analysis. The N-protein peptide N220 shows a high binding affinity towards human MHC class I in T2-cells, and is capable of activating cytotoxic T-cells in human peripheral blood mononuclear cells (PBMCs). The application of using the N220 peptide sequence with a single-chain-trimer (SCT) approach to produce a potential DNA vaccine candidate was investigated in HLA-A2.1K(b) transgenic mice. Cytotoxicity assay clearly showed that the T-cells obtained from the vaccinated animals were able to kill the N-protein expressing cells with a cytotoxicity level of 86% in an effector cells/target cells ratio of 81:1 one week after the last vaccination, which is significantly higher than other N-protein peptides previously described. The novel immunogenic N-protein peptide revealed in the present study provides valuable information for therapeutic SARS vaccine design.

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“…The T2 cell-binding assay has been described previously (8,44). Briefly, to measure the dissociation rate of peptides from HLA-A*0201, T2 cells incubated with RPMI 1640 containing 5% fetal bovine serum were mixed with peptide (10 g/ml RPMI containing 5% fetal bovine serum) and human ␤2-microglobulin (5 g/ml) for 20 h at 26°C and subsequently shifted to 37°C for 2 h. Then, the cells were stained for HLA-A*0201 expression with fluorescein isothiocyanate (FITC)-labeled anti-human HLA-A*0201 (BD Biosciences Pharmingen, San Diego, CA), fixed with 1% paraformaldehyde, and analyzed by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

“…HLA-A*0201 transgenic mice were purchased and imported from the Jackson Laboratory (Bar Harbor, ME) and maintained in our institute under specific-pathogen-free conditions. The transgenic mice with C57BL/6 background expressing major histocompatibility complex class I (MHC-I) molecules of human HLA-A*0201 have been described previously (7,44). Splenocytes from peptide-vaccinated HLA-A*0201 transgenic mice or controls were incubated for 12 h with stimulator (HPV-16 E5 synthetic peptides) for the detection of E5 peptide-specific CD8 ϩ T-cell precursors.…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic T-Lymphocyte Responses to Human Papillomavirus Type 16 E5 and E7 Proteins and HLA-A*0201-Restricted T-Cell Peptides in Cervical Cancer Patients

Liu

Yang

Lin

et al. 2007

J Virol

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Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a tumor rejection antigen and can induce cytotoxic T-lymphocyte (CTL) activity. Therefore, in this study, human leukocyte antigen A*0201 (HLA-A*0201)-restricted human CTL epitopes of HPV-16 E5 protein were identified using a bioinformatics approach, and the abilities of these predicted peptides to induce an immune response in HLA-A*0201 transgenic mice were confirmed by assaying E5-specific CTLs and in vitro-generated CTLs from normal peripheral blood T lymphocytes of HLA-A2-positive human donors. Second, the CTL responses to HLA-A*0201 CTL epitopes (E5 63-71 and E7 11-20) were examined in HPV-16-infected patients with HLA-A2. Third, the effect of HLA-A-type alleles on CTL activities in response to the entire E5 and E7 proteins was examined in cervical cancer patients. E5 and E7 peptides (but not the whole proteins) stimulated E5-and E7-specific CTL recall responses in HPV-16-and HLA-A2-positive cervical cancer patients, and HPV-16 E5 and E7 proteins stimulated naïve T cells in HPV-16-negative cervical cancer patients with HLA-A11 and -A24 haplotypes. In summary, this is the first demonstration that E5 63-71 is an HLA-A*0201-restricted T-cell epitope of HPV-16 E5.Cervical cancer accounts for almost 12% of all cancers in women and thus represents the second most frequent gynecological malignancy in the world (50). Cervical cancer is caused by specific human papillomavirus (HPV) infections. HPV type 16 (HPV-16) is the predominant etiologic agent of cervical cancer and carries three transforming oncogenes, E5, E6, and E7. E6 and E7 expression has been found in cervical cancer cell lines and cancer biopsy specimens, and the two proteins play roles in malignant transformation. They are independently able to immortalize various human cell types in tissue culture, but the efficiency of transformation is increased when they are coexpressed (50).HPV-16 E5 protein stimulates cell growth by forming a complex with the epidermal growth factor receptor, ErbB4, platelet-derived growth factor receptor, and colony-stimulating factor 1 receptor (12,16,41,50). In vivo studies have demonstrated that E5 is expressed soon after infection. E5 mRNA and protein are detectable in low-grade squamous intraepithelial lesions (2, 9), and the prevalence of E5-containing mRNA increases with the advancing severity of disease (2). However, as HPV-infected lesions progress to cervical cancer, episomal viral DNA frequently becomes integrated into the host cell DNA, and a substantial part of the genome, commonly including the E5 coding sequence, is deleted (16,41,50). Thus, E5 expression is not obligatory in late events of HPV-mediated carcinogenesis.The viral oncoproteins are unique tumor antigens and can be ideally used as tumor vaccines (32, 33). HPV-16 E5, E6, and E7 have been experimentally identified as target antigens by immune intervention protocols against cervical cancer. Evidence for increased tumor incidence in T-cell-immunosuppressed patients strongly suggest...

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HLA-A∗0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

Cited by 57 publications

References 38 publications

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope

Cytotoxic T-Lymphocyte Responses to Human Papillomavirus Type 16 E5 and E7 Proteins and HLA-A*0201-Restricted T-Cell Peptides in Cervical Cancer Patients

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