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

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. 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. 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 <0.05). The HPV-16 E7 peptide-specific CD4+ 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.