HLA-DQB1*02 - restricted HPV-16 E7 peptide - specific CD4+ T-Cell immune responses correlate with regression of HPV-16- associated high-grade squamous intraepithelial lesions

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Abstract

Purpose: The fact that up to 30% of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. Experimental Design: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. Results: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value + T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.

Original languageEnglish (US)
Pages (from-to)2479-2487
Number of pages9
JournalClinical Cancer Research
Volume13
Issue number8
DOIs
StatePublished - Apr 15 2007

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Human papillomavirus 16
T-Lymphocytes
Peptides
Epitopes
T-Lymphocyte Epitopes
Uterine Cervical Neoplasms
Lymphocytes
Amino Acids
Papillomavirus Vaccines
HLA-DQB1 antigen
Squamous Intraepithelial Lesions of the Cervix
Research Design
Maintenance
Tissue Donors
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{108ac797bf674864926365f9a3d83e66,
title = "HLA-DQB1*02 - restricted HPV-16 E7 peptide - specific CD4+ T-Cell immune responses correlate with regression of HPV-16- associated high-grade squamous intraepithelial lesions",
abstract = "Purpose: The fact that up to 30{\%} of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. Experimental Design: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. Results: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value + T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.",
author = "Shiwen Peng and Trimble, {Cornelia L} and Wu, {Lee Shu Fune} and Pardoll, {Andrew Mark} and Roden, {Richard S} and Chien-Fu Hung and Wu, {Tzyy Choou}",
year = "2007",
month = "4",
day = "15",
doi = "10.1158/1078-0432.CCR-06-2916",
language = "English (US)",
volume = "13",
pages = "2479--2487",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",

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TY - JOUR

T1 - HLA-DQB1*02 - restricted HPV-16 E7 peptide - specific CD4+ T-Cell immune responses correlate with regression of HPV-16- associated high-grade squamous intraepithelial lesions

AU - Peng, Shiwen

AU - Trimble, Cornelia L

AU - Wu, Lee Shu Fune

AU - Pardoll, Andrew Mark

AU - Roden, Richard S

AU - Hung, Chien-Fu

AU - Wu, Tzyy Choou

PY - 2007/4/15

Y1 - 2007/4/15

N2 - Purpose: The fact that up to 30% of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. Experimental Design: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. Results: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value + T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.

AB - Purpose: The fact that up to 30% of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. Experimental Design: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. Results: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value + T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.

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U2 - 10.1158/1078-0432.CCR-06-2916

DO - 10.1158/1078-0432.CCR-06-2916

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AN - SCOPUS:34247882038

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SP - 2479

EP - 2487

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 8

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