Human Leukocyte Antigen-A2.1 Restricted Candidate Cytotoxic T Lymphocyte Epitopes of Human Papillomavirus Type 16 E6 and E7 Proteins Identified by Using the Processing-Defective Human Cell Line T2

Kast, W. Martin; Brandt, R. M. P.; Drijfhout, Jan W.; Melief, Cornelis J.M.

doi:10.1097/00002371-199308000-00006

Cited by 87 publications

(89 citation statements)

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“…Tetramers were purchased from Coulter (Krefeld, Germany) and included the following HLA-A2.1-binding peptides: GILGFVFTL, an influenza matrix immunodominant peptide (residues 58-66); ILKEPVHGV, the HIV-1 reverse transcriptase peptide (pol 476-484); YMLDLQPETT, corresponding to HPV16 E7 [11][12][13][14][15][16][17][18][19][20] ; LLMGTLGIV, corresponding to HPV16 E7 82-90 or TLGIVCPI, corresponding to HPV16 E7 [86][87][88][89][90][91][92][93] .…”

Section: Tetrameric Peptide-mhc Class I Complexes (Tetramers)mentioning

confidence: 99%

“…HPV16 E7 11-20 and HPV16 E7 86-93 specific T cells were expandable upon IVS with cognate peptide-pulsed DC and were reactive against peptide-pulsed targets or, in case of the E7 11-20 epitopespecific T cells, against HPV16 E7 expressing CaSki cell line. Thus, in patients with HPV16 1 SCCO, precursor T cells specific for E7 [11][12][13][14][15][16][17][18][19][20] epitope are present (1/3,947) in the circulation, are responsive to stimulation with the cognate viral peptide and recognize in vitro HPV16 E7 1 tumor cells. Further studies have to elucidate why those T cells are unable to eliminate the tumor in vivo and this might also allow for finding potential strategies that will increase the chances of developing a future HPV-based vaccine in patients with SCCO. '…”

mentioning

confidence: 99%

“…16,17 To generate HPV16 E7-specific tetramers, immunogenic peptides had to be selected. To date, only a few human leukocyte antigen (HLA)-A2.1 restricted HPV16 E7-derived peptides, HPV16 E7 [11][12][13][14][15][16][17][18][19][20] , HPV16 E7 82-90 and HPV16 E7 [86][87][88][89][90][91][92][93] , have been shown to be immunogenic in cervical carcinomas. [18][19][20][21][22][23][24][25] We, therefore, selected these peptides for the production of tetramers to be used for the quantification of HPV16 E7-specific T cells in the peripheral blood of SCCO patients and normal controls.…”

mentioning

confidence: 99%

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T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

Hoffmann

Arsov

Schirlau

et al. 2005

Intl Journal of Cancer

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Squamous cell carcinomas of the oropharynx (SCCO) are often infected with oncogenic human papilloma virus (HPV) subtype 16. To determine the frequency of T cells specific for human leukocyte antigen (HLA)-A2.1 restricted HPV16 E7 protein-derived epitopes, tetramer analysis was performed using peripheral blood lymphocytes of 20 HLA-A2.1 1 patients and 20 HLA-A2.1 1 healthy individuals. Tetramers specific for 3 HPV16 peptides (E7 11-20 , E7 82-90 and E7 86-93) , an influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel antigen) were used in multicolor flow analysis. The HPV-specific T-cell frequencies were correlated with the HPV16 E7 and p16 status in tumor sections. In vitro stimulation (IVS) with autologous dendritic cells (DC) pulsed with HPV16 E7 epitopes was performed to demonstrate proliferation and antitumor activity of the HPV-responsive T cells. Frequencies of CD8 1 T cells specific for HPV16 E7 peptides were not significantly different in patients with SCCO relative to normal donors. However, patients with tumors expressing HPV16 E7 (60%) and p16 (50%) had an increased frequency (p < 0.05) of T cells specific for the E7 11-20 epitope compared to those with tumors negative for both markers. HPV16 E7 11-20 and HPV16 E7 86-93 specific T cells were expandable upon IVS with cognate peptide-pulsed DC and were reactive against peptide-pulsed targets or, in case of the E7 11-20 epitopespecific T cells, against HPV16 E7 expressing CaSki cell line. Thus, in patients with HPV16 1 SCCO, precursor T cells specific for E7 [11][12][13][14][15][16][17][18][19][20] epitope are present (1/3,947) in the circulation, are responsive to stimulation with the cognate viral peptide and recognize in vitro HPV16 E7 1 tumor cells. Further studies have to elucidate why those T cells are unable to eliminate the tumor in vivo and this might also allow for finding potential strategies that will increase the chances of developing a future HPV-based vaccine in patients with SCCO. ' 2005 Wiley-Liss, Inc.Key words: HPV; specific T cells; head and neck cancer; tetramer Squamous cell carcinomas (SCC) represent the most common type of head and neck cancer, accounting for 6% of all new cancer cases. 1 Typical risk factors include alcohol and nicotine consumption. However, a significant proportion of the patients do not have these risk factors, and recent studies have suggested an association of SCC to viral pathogens such as high risk (oncogenic) human papilloma virus (HPV) types, particularly HPV16 or 18. These viruses are frequently found in squamous carcinoma of the head and neck. 2-11 HPV16 infections have been observed in approximately one half of squamous cell carcinomas of the oropharynx (SCCO). 7,[10][11][12] The HPV16 1 SCCO have a good prognosis and are not associated with conventional risk factors, suggesting they may represent a separate tumor entity. 3,7,10,11 The HPV-derived oncoproteins E6 and E7 are mainly responsible for both the onset and maintenance of malignant transforma...

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Section: Tetrameric Peptide-mhc Class I Complexes (Tetramers)mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

Hoffmann

Arsov

Schirlau

et al. 2005

Intl Journal of Cancer

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“…In this library, consequently, all possible epitope sequences of the HPV18 E7 were represented. Sequences are: HPV18 E7 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , p44 (MHGP-KATLQDIVLHLEPQNE); HPV18 E7 [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] , p45 (VLHLEPQNE-IPVDLLCHEQL); HPV18 E7 , p46 (VDLLCHEQLSDSEEEN-DEID); HPV18 E7 34 -53 , p47 (SEEENDEIDGVNHQHLPARR); HPV18 E7 [45][46][47][48][49][50][51][52][53]…”

Section: Peptides and Proteinsmentioning

confidence: 99%

“…Mean fluorescence of HLA-A2-positive cells, which is proportional to the binding strength of the peptide was assessed in a FACS Calibur and mean values of triplicates were calculated. 31 …”

Section: T2 Peptide Binding Assaymentioning

confidence: 99%

Identification of a naturally processed HLA‐A0201 HPV18 E7 T cell epitope by tumor cell mediated in vitro* vaccination

Kather

Ferrara

Nonn

et al. 2003

Intl Journal of Cancer

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Immunotherapy of HPV-associated disease such as cervical cancer is moving from preclinical investigation to clinical trials. The viral oncoproteins E6 and E7 are ideal target antigens because their expression is mandatory in HPVtransformed tumor cells. T cells are the most important effector cells for therapeutic vaccination strategies. Therefore, the identification and characterization of HPV E6 and E7 T cell epitopes is necessary. Methods to date rely on screening for immunogenicity of peptides predicted by algorithms. Presentation of the identified peptides on tumor cells, however, needs to be confirmed. In our study, we have improved the method to identify peptide epitopes of HPV18 E7 that are actually presented by tumor cells. We induced allogeneic T-cell lines by stimulation with HPV18-positive, CD80 and HLA-A*0201 transfected cervical cancer cells. Sensitized T cells were probed against an array of a HPV18 E7 20mer peptide-library. We found specific reactivity to one of the 20mer peptides. This sequence was then screened via algorithms for putative epitopes. One putative HLA-A2 restricted epitope was confirmed to bind to HLA-A2, to be immunogenic and to induce IFN␥-release in ELISpot assays. Epitope-specific T cells were cytolytic toward autologous peptide pulsed targets and HPV18 transformed tumor cells. The identification of epitope-specific T cells in tumor infiltrating lymphocytes of a HPV18-positive HLA-matched cervical cancer patient suggests an in vivo relevance of the identified epitope. We suggest that our approach is advantageous over conventional methods, because it yields candidate peptides that are relevant CTL epitopes that are expressed, processed and presented by tumor cells.

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Induction of human cytotoxic T lymphocytes specific for prostate-specific antigen

et al. 1997

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Human Leukocyte Antigen-A2.1 Restricted Candidate Cytotoxic T Lymphocyte Epitopes of Human Papillomavirus Type 16 E6 and E7 Proteins Identified by Using the Processing-Defective Human Cell Line T2

Cited by 87 publications

References 0 publications

T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

Identification of a naturally processed HLA‐A0201 HPV18 E7 T cell epitope by tumor cell mediated in vitro* vaccination

Induction of human cytotoxic T lymphocytes specific for prostate-specific antigen

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Human Leukocyte Antigen-A2.1 Restricted Candidate Cytotoxic T Lymphocyte Epitopes of Human Papillomavirus Type 16 E6 and E7 Proteins Identified by Using the Processing-Defective Human Cell Line T2

Cited by 87 publications

References 0 publications

T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

Identification of a naturally processed HLA‐A*0201 HPV18 E7 T cell epitope by tumor cell mediated in vitro vaccination

Induction of human cytotoxic T lymphocytes specific for prostate-specific antigen

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Product

Resources

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Identification of a naturally processed HLA‐A0201 HPV18 E7 T cell epitope by tumor cell mediated in vitro* vaccination