PMID- 10096544
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20101118
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 6
DP  - 1999 Mar 15
TI  - Induction of specific CD8+ T-lymphocyte responses using a human papillomavirus-16 
      E6/E7 fusion protein and autologous dendritic cells.
PG  - 1184-7
AB  - When intracellular viral proteins are degraded, only a limited number of peptide 
      epitopes are capable of eliciting specific CD8+ cellular immune responses for a 
      given human leukocyte antigen (HLA) haplotype. We sought to induce CD8+ 
      T-lymphocyte (CTL) responses to human papillomavirus-16 (HPV-16) E6 and E7 
      proteins using a recombinant E6/E7 fusion protein and autologous human dendritic 
      cells (DCs). CTLs were generated by in vitro stimulation using a recombinant 
      HPV-16 E6/E7 fusion protein and autologous DCs from a healthy HLA-A*0201 donor. 
      CTL specificity was assessed by cytokine release assays when the cells were 
      reacted with autologous DC targets coincubated with the E6/E7 fusion protein. 
      These CTLs were also reacted with the immunodominant E7 peptides (E711-20 and 
      E7(86-93)) and DCs as a target. As a negative control, DCs were incubated with or 
      without an irrelevant control protein (Helicobacter pylori) as target for the 
      E6/E7-induced CTLs. The E6/E7-induced CTLs were capable of specific recognition 
      of target DCs coincubated with E6/E7 but not the control protein. When 
      E6/E7-specific CTLs were reacted with DCs and either E7(11-20) or E7(86-93), 
      specific peptide recognition was also detected. These data demonstrate that 
      specific CTLs can be elicited using autologous human DCs and a HPV-16 E6/E7 
      fusion protein. Therefore, extracellular viral proteins seem to be engulfed and 
      processed by DCs; then the immunodominant HLA-A2-restricted peptides become 
      available for CD8+ T-lymphocyte recognition. These data suggest that vaccine 
      strategies using recombinant viral proteins may overcome the limitation of 
      peptide epitopes for specific HLA haplotypes and may, therefore, permit more 
      generalized clinical application.
FAU - Murakami, M
AU  - Murakami M
AD  - Section of Gynecologic Oncology, Surgery Branch, Division of Clinical Sciences, 
      National Cancer Institute, Bethesda, Maryland 20892, USA.
FAU - Gurski, K J
AU  - Gurski KJ
FAU - Marincola, F M
AU  - Marincola FM
FAU - Ackland, J
AU  - Ackland J
FAU - Steller, M A
AU  - Steller MA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Histocompatibility Antigens Class I/biosynthesis/immunology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Lymphocyte Subsets/immunology
MH  - Oncogene Proteins, Viral/*immunology
MH  - Papillomavirus E7 Proteins
MH  - Recombinant Fusion Proteins/immunology
MH  - *Repressor Proteins
EDAT- 1999/03/30 00:00
MHDA- 1999/03/30 00:01
CRDT- 1999/03/30 00:00
PHST- 1999/03/30 00:00 [pubmed]
PHST- 1999/03/30 00:01 [medline]
PHST- 1999/03/30 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Mar 15;59(6):1184-7.