title: Proliferative T cell responses to the human papillomavirus type 16 E7 protein in women with cervical dysplasia and cervical carcinoma and in healthy individuals.
abstract: The levels of proliferative T cell responses to peptides representing the human papillomavirus type 16 (HPV-16) E7 protein have been measured using short-term T cell lines derived from peripheral blood of healthy women and those with cervical dysplasias and carcinoma of the cervix. In healthy individuals 47 percent (7/15) responded predominantly to the N- and C-terminal regions of the protein and 6/7 responders were to a single peptide between amino acids 80-94. In comparison 29 percent (9/31) of women with cervical dysplasia responded to HPV-16 E7, with a significantly reduced response to both the N- and C-terminal regions (P = 0.03 and 0.038, respectively). A higher proportion of responders was found in patients with high grade lesions (56 percent, 5/9) versus those with atypical or low grade histology (20 percent, 4/20) and the response to a single peptide between amino acids 75-94 was also increased in this patient group (P = 0.044). This may be a reflection of higher levels of current or previous exposure to HPV-16 in patients with high grade lesions. Correlation of T cell responses with HPV DNA type (detected by PCR of cervical biopsy tissue) showed that 3/9 (33 percent) HPV-16 DNA-positive individuals responded. This suggests that E7 may not be the dominant target of the immune response or that the response to E7 is down-regulated in these patients. In addition 4/18 (22 percent) HPV-16 DNA-negative individuals responded, suggesting that their T cells may have been primed by previous exposure to HPV-16 or that a cross-reactive response was detected. Proliferative T cell responses to both HPV-16 E7 and L1 were reduced in women with cervical carcinoma in comparison to those with cervical dysplasia and healthy controls. The observed down-regulation of responses to HPV-16 E7 in women with cervical dysplasia and cervical carcinoma may reflect an altered functional balance between subsets of T helper cells in HPV-16 infections.
authors: Department of Immunology, Guy's Hospital Medical School, London, UK.
authors: J C
authors: JC
authors: Luxton
authors: A J
authors: AJ
authors: Rowe
authors: J C
authors: JC
authors: Cridland
authors: T
authors: T
authors: Coletart
authors: P
authors: P
authors: Wilson
authors: P S
authors: PS
authors: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D036022:Capsid Proteins; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16