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Stephen Man

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Table 3. Reported studies of human CD8+ cytotoxic T-cell responses that are specific for human papillomaviruses (HPVs) (tab003smc)
Study and assay detailsa Comments
(Ref. 68) Ressing et al. (1995)
Re-stimulation: HPV-16 E7 peptides bound to HLA-A*0201 on activated B cells or T2 cells.
Detection: Peptide on B-LCL, or CaSki cells (HPV-16-transformed cervical keratinocytes);
T-cell specificity: HPV-16 E7.		 Controls: 6/9 responded. CTLs were CD8+. HPV-16-peptide-specific CTLs recognised HPV-16 E7 expressed on CaSki cells. CTL responses were likely to be primary responses (they were obtained from healthy donors who had no HPV disease).
(Ref. 50) Ressing et al. (1996)
Re-stimulation: HPV-16 E7 peptides bound to HLA-A*0201 on PBMCs.
Detection: Peptide on B-LCL, or CaSki cells.
T-cell specificity: HPV-16 E7.		 Women with CIN3 and who were HPV-16+: 2/11 responded. Women with CaCx and who were HPV-16+: 2/11 responded. Controls: 0/10 responded. CTL responses in patients were likely to be memory-CTL responses because the donors were HPV-16+. CTL responses against influenza M1 peptide decreased in CaCx patients compared with women with CIN3 and controls.
(Ref. 53) Evans et al. (1996)
Re-stimulation: CaSki cells (HLA-A*0201-).
Detection: HPV-16 E6 or E7 genes transfected into C33A cells or CaSki cells.
T-cell specificity: HPV-16 E7 and E6.		 Women with CIN2 and who were HPV-16+: 1/11 responded. No normal controls tested.
(Ref. 51) Evans et al. (1997)
Re-stimulation: HPV-16 E7 peptides [or mitogen (PHA)] bound to HLA-A*0201 on PBMCs.
Detection: Peptide on B-LCL, or B-LCL cells infected with r vaccinia-HPV (expressing early proteins), or Caski cells.
T-cell specificity: HPV-16 E7. HPV-16 E6/E7. HPV-18 E6/E7.		 Women with CaCx and who were HPV-16+ and HPV-31+: 4/5 responded. Controls: 0/4 responded. After using peptides to stimulate CTLs in vitro, T-cell responses were detected against HPV-16 E7 peptides. 3/4 CaCx patients were tested for HPVs; 2 were HPV-16+, 1 was HPV-31+. HPV-16-peptide-specific CTLs recognise B-LCL infected with r vaccinia-HPV. CTLs recognising full-length HPV-16 E6/E7 or HPV-18 E6/E7 could be detected among tumour-infiltrating lymphocytes.
(Ref. 55) Nimako et al. (1997)
Re-stimulation: HPV-16 E6/E7 or HPV-18 E6/E7 protein (expressed in recombinant adenoviruses) on multiple HLA types on PHA blasts.
Detection: B-LCL infected by r vaccinia-HPV (expressing early proteins), or CaSki cells.
T-cell specificity: HPV-16 E6/E7. HPV-18 E6/E7.		 Women with CIN3 and who were HPV-16+: 6/10 responded. Controls: 0/10 responded. The HPV-specific CTLs obtained recognised both r vaccinia-HPV and CaSki. Three of the women with CIN3 had evidence of infection with HPV-16. Multiple HLA class I restriction patterns were seen.
(Ref. 52) Jochmus et al. (1997)
Re-stimulation: HPV-16 E7 peptides bound to HLA-A*0201 on dendritic cells (as APCs).
Detection: HPV-16 E7 peptides or SIHA cells and CaSki cells.
T-cell specificity: HPV-16 E7.		 Controls: 1/1 responded. Woman with CIN3 and who were HPV-16+: 1/1 responded. CTLs specific for HPV-16 E7 peptide could be derived using only dendritic cells as APCs. Likely to be a primary CTL response. CTLs were unable to recognise full-length HPV-16 E7 protein.
(Ref. 54) Nakagawa et al. (1997)
Re-stimulation: HPV-16 E6 and E7 proteins on multiple HLAs on PBMCs.
Detection: B-LCL infected with r vaccinia-HPV (expressing early proteins).
T-cell specificity: HPV-16 E7. HPV-16 E6.		 Women who were HPV-16 but did not have CIN: 6/8 responded. Women with CIN and who were HPV-16+: 2/7 responded. HPV-specific CTL responses occurred more frequently in HPV-16-infected patients without CIN.
(Ref. 69) Konya et al. (1997)
Re-stimulation: HPV-16 E2 peptides binding to HLA-A*0201 on PBMCs as APCs.
Detection: HPV-16 E2 peptides or HPV-16-transfected cell line.
T-cell specificity: HPV-16 E2.		 Controls: 2/3 responded. CTLs that were specific for HPV-16 E2 peptide could recognise full-length HPV-16 E2. CTL responses were likely to be primary responses because they were obtained from healthy donors without HPV disease.

a Re-stimulation = source of HPV-derived antigen (or mitogen) used to re-stimulate (or stimulate) responding T cells, and source of antigen-presenting cells and their HLA type; Detection = source of HPV-derived antigen, and source of target cells; T-cell specificity = HPV-derived antigen that the responding T cells were specific for.

Abbreviations used: APC = antigen-presenting cell; B cells = B lymphocytes; B-LCL = B-lymphoblastoid cell line (B cells transformed by Epstein–Barr virus); CaCx = cervical cancer; CaSki = HPV-16-transformed cervical keratinocyte line, which expresses HLA-A*0201; CD8 = cell-surface receptor characteristic of cytotoxic T cells (CTLs); CIN = cervical intraepithelial neoplasia; CIN3 = cervical intraepithelial neoplasia stage 3, the most advanced stage before invasion; C33A = cervical keratinocyte line, which is HPV16- and HLA-A*0201+; E2, E6, E7 = HPV early proteins; HLA = human leukocyte antigen, which is the human form of the major histocompatibility complex (MHC); PHA blasts = PBMCs stimulated by PHA; PBMCs = peripheral blood mononuclear cells; PHA = phytohaemagglutinin; r vaccinia-HPV = recombinant vaccinia virus expressing HPV proteins; SIHA = HPV-16-transformed cervical keratinocyte cell line; T2 = human cell line that is defective for antigen processing but good at presenting peptides.

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