OCCASIONAL MEMORY CYTOTOXIC T-CELL RESPONSES OF PATIENTS WITH HUMAN PAPILLOMAVIRUS TYPE 16-POSITIVE CERVICAL LESIONS AGAINST A HUMAN-LEUKOCYTE ANTIGEN-A-ASTERISK-0201-RESTRICTED E7-ENCODED EPITOPE

Most cervical carcinoma (Cxca) cells constitutively express human papi llomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy, Previou sly, we identified HPV16 E7-encoded CTL epitopes, In patients with cer vical intraepithelial neoplasia or Cxca, little is known concerning T- cell activity against viruses in general and against HPV16 in particul ar, Here, we have screened the blood of 10 healthy donor controls and of 22 patients with HPV16(+) cervical lesions for the presence of CTLs directed against HPV16 E7- and control influenza virus matrix-derived epitopes presented by HLA-A0201, We detected influenza virus-specifi c CTLs in all donors and in the majority of patients, indicating that most patients have functioning T-cell responses despite their lesions or therapeutic interventions, Moreover, we show that patients with HPV 16(+) lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLDLQPETT), providing evidence for natural CTL imm unity against HPV16 in patients with cervical lesions. Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded pe ptides to induce or augment CTL responses for treatment or prevention of Cxca.