Occasional memory cytotoxic T-cell responses of patients with human papillomavirus type 16-positive cervical lesions against a human leukocyte antigen-A *0201-restricted E7-encoded epitope.
Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy. Previously, we identified HVP16 E7-encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or Cxca, little is known concerning T-cell activity against viruses in general and against HPV16 in particular. 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-A *0201. We detected influenza virus-specific 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 HPV16+ lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural CTL immunity against HPV16 in patients with cervical lesions. Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded peptides to induce or augment CTL responses for treatment or prevention of Cxca.
Ressing
M E
ME
Department of Immunohematology, University Hospital Leiden, The Netherlands.
van Driel
W J
WJ
Celis
E
E
Sette
A
A
Brandt
M P
MP
Hartman
M
M
Anholts
J D
JD
Schreuder
G M
GM
ter Harmsel
W B
WB
Fleuren
G J
GJ
Trimbos
B J
BJ
Kast
W M
WM
Melief
C J
CJ
D000595:Amino Acid Sequence; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology
D000939:Epitopes; D015234:HLA-A Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16