PROLIFERATIVE T-CELL RESPONSES TO THE HUMAN PAPILLOMAVIRUS TYPE-16 E7PROTEIN IN WOMEN WITH CERVICAL DYSPLASIA AND CERVICAL-CARCINOMA AND IN HEALTHY-INDIVIDUALS

The levels of proliferative T cell responses to peptides representing the human papillomavirus type 16 (HPV-16) E7 protein have been measure d using short-term T cell lines derived from peripheral blood of healt hy women and those with cervical dysplasias and carcinoma of the cervi x. In healthy individuals 47% (7/15) responded predominantly to the N- and C-terminal regions of the protein and 6/7 responders were to a si ngle peptide between amino acids 80-94, In comparison 29% (9/31) of wo men with cervical dysplasia responded to HPV-16 E7, with a significant ly reduced response to both the N- and C-terminal regions (P = 0.03 an d 0.038, respectively), A higher proportion of responders was found in patients with high grade lesions (56%, 5/9) versus those with atypica l or low grade histology (20%, 4/20) and the response to a single pept ide 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, Corre lation of T cell responses with HPV DNA type (detected by PCR of cervi cal biopsy tissue) showed that 3/9 (33%) HPV-16 DNA-positive individua ls responded, This suggests that 67 may not be the dominant target of the immune response or that the response to E7 is downregulated in the se patients, In addition 4/18 (22%) HPV-16 DNA-negative individuals re sponded, suggesting that their T cells may have been primed by previou s exposure to HPV-16 or that a crossreactive response was detected. Pr oliferative T cell responses to both HPV-16 E7 and L1 were reduced in women with cervical carcinoma in comparison to those with cervical dys plasia and healthy controls, The observed down-regulation of responses to HPV-16 67 in women with cervical dysplasia and cervical carcinoma may reflect an altered functional balance between subsets of T helper cells in HPV-16 infections.