Analysis of HLA‐DRB1*0901‐binding HPV‐16 E7 helper T cell epitope†

Okubo, Mitsuo; Saito, Maki; Inoku, Hiroki; Hirata, Ranko; Yanagisawa, Masami; Takeda, Satoru; Kinoshita, Katsuyuki; Maeda, Hitoshi

doi:10.1111/j.1447-0756.2003.00171.x

Cited by 5 publications

(2 citation statements)

References 43 publications

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“…On the other hand, only a handful of HPV-specific CD4 T-cell epitopes have been described [i.e., E7 50-62 (33 amino acids long) restricted by DR15, E7 43-77 (35 amino acids long) restricted by DR3, and E7 35-50 (16 amino acids long) restricted by DQ2 described by van der Burg et al [30]; and E7 61-80 (20 amino acids long) restricted by DR9 described by Okubo et al [19]. Recently, Gallagher and Man described one HPV 16 E6 CD4 epitope (E6 127-141 restricted by HLA-DRB1*01) and one HPV 18 E6 CD4 epitope (E6 43-57 restricted by HLA-DRB1*15) [8].…”

Section: Discussionmentioning

confidence: 99%

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

Wang

Santin

Bellone

et al. 2008

Cancer Immunol Immunother

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Previously, safety and immunogenicity of human papillomavirus type 16 (HPV16) or 18 E7-pulsed dendritic cells (DC) vaccinations were demonstrated in a dose-escalation Phase I clinical trial which enrolled ten patients diagnosed with stage IB or IIA cervical cancer (nine HPV 16-positive, one HPV 18-positive). The goal of the study was to define the T-cell epitopes of HPV 16 or 18 E7 protein in these patients in order to develop new strategies for treating HPV-associated malignancies. This was accomplished through establishing T-cell lines by stimulating peripheral blood mononuclear cells with autologous mature DC pulsed with the HPV 16 or 18 E7 protein, examining the T-cell responses using ELISPOT assays, and isolating E7-specific T-cell clones based on IFN-γ secretion. Then, the epitope was characterized in terms of its core sequence and the restriction element. Twelve T-cell lines from eight subjects (seven HPV 16-positive, one HPV 18-positive) were evaluated. Positive Tcell responses were demonstrated in four subjects (all HPV 16-positive). All four were positive for the HPV 16 E7 46-70 (EPDRAHYNIVTFCCKCDSTLRLCVQ) region. T-cell clones specific for the E7 47-70 region were isolated from one of the subjects. Further analyses revealed a novel, naturally processed, CD4 T-cell epitope, E7 58-68 (CCKCDSTLRLC), restricted by the HLA-DR17 molecule.

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Section: Discussionmentioning

confidence: 99%

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

Wang

Santin

Bellone

et al. 2008

Cancer Immunol Immunother

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“…1d). A Th2 skew during disease progression, and therefore in the presence of antigen persistence, was also reported for HPV‐16 E7‐specific CD4 + T cells 34,35 . Interestingly, strong anti‐E7 CD4 + T‐cell immunity was observed in both HPV‐18 − patients and healthy donors, in whom presumably immunization occurred in the presence of the episomal form of the virus, suggesting a possible role for viral integration in the impairment of anti‐E7 immunity in HPV‐18 + patients.…”

Section: Discussionmentioning

confidence: 53%

CD4⁺ T cells against human papillomavirus‐18 E7 in patients with high‐grade cervical lesions associate with the absence of the virus in the cervix

et al. 2010

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IntroductionCervical cancer is the second most common cancer in women worldwide and is associated with human papillomavirus (HPV) persistent infection. [1][2][3] In fact, HPV is detected in > 99% of cervical cancer and is now considered the primary aetiological agent in cervical cancer tumorigenesis.4 Development of HPV-related neoplastic lesions, from cervical intraepithelial neoplasia (CIN) to cervical carcinoma, is the result of infection by high-risk HPV, during which integration of the viral episome into the host-cell DNA frequently occurs. The two most common genotypes found in the lesions are HPV-16 and HPV-18, with a prevalence of 50-60% and 15-18%, respectively.

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Whole-Genome Analysis of Human Papillomavirus Types 16, 18, and 58 Isolated from Cervical Precancer and Cancer Samples in Chinese Women

Liu

Pan

Gao

et al. 2017

Sci Rep

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Human papillomavirus (HPV) types 16, 18 and 58 are ranked the top three high-risk HPV types for cervical intraepithelial neoplasia (CIN) and invasive carcinoma. We aimed to evaluate the diversity of HPV16, HPV18, and HPV58 genetic variants by HPV capture technology combined with next generation sequencing. 295, 73, and 148 variations were observed in 51 HPV16, 7 HPV18, and 11 HPV58 genomes, respectively. HPV16 isolates were predominantly of the A variant lineage, and sublineage A4 (Asian) was the most common. However, there were no significant differences in the distribution of HPV16 A1–3 and A4 variants between CIN1-, CIN2/3, and cervical cancer groups. The 7 HPV18 genomes were assigned to the A3/A4 and A1 sublineages. Of the 11 HPV58 genomes, the most predominant variant sublineages were A2, followed by A1 and B2. The majority of HPV16/18 samples containing contiguous genomic deletions were found to harbor HPV integration. Some T-cell epitope sequences in HPV16 E6 and E7 showed considerable divergence from the prototype NC_001526, suggesting their importance in immunotherapy of HPV-associated carcinomas. In conclusion, sequence diversity and phylogenies of HPV16, 18, and 58 provide the basis for future studies of discrete viral evolution, epidemiology, pathogenicity, and the differences in response to vaccines.

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Analysis of HLA‐DRB1*0901‐binding HPV‐16 E7 helper T cell epitope†

Abstract: Thus HPV-16 E7d peptide as an HLA-DRB1*0901-restricted helper T cell epitope might usefully be incorporated into an understanding of the immunological mechanism and immunotherapy for this disease.

Cited by 5 publications

References 43 publications

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

CD4⁺ T cells against human papillomavirus‐18 E7 in patients with high‐grade cervical lesions associate with the absence of the virus in the cervix

Whole-Genome Analysis of Human Papillomavirus Types 16, 18, and 58 Isolated from Cervical Precancer and Cancer Samples in Chinese Women

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Analysis of HLA‐DRB1*0901‐binding HPV‐16 E7 helper T cell epitope†

Abstract: Thus HPV-16 E7d peptide as an HLA-DRB1*0901-restricted helper T cell epitope might usefully be incorporated into an understanding of the immunological mechanism and immunotherapy for this disease.

Cited by 5 publications

References 43 publications

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

CD4+ T cells against human papillomavirus‐18 E7 in patients with high‐grade cervical lesions associate with the absence of the virus in the cervix

Whole-Genome Analysis of Human Papillomavirus Types 16, 18, and 58 Isolated from Cervical Precancer and Cancer Samples in Chinese Women

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CD4⁺ T cells against human papillomavirus‐18 E7 in patients with high‐grade cervical lesions associate with the absence of the virus in the cervix