Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens
Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altere...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00075/full |
| _version_ | 1811193357286768640 |
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| author | Derin B Keskin Derin B Keskin Bruce eReinhold Bruce eReinhold Sun Young eLee Guanglan eZhang Guanglan eZhang Simon eLank David eO'Connor Ross S Berkowitz Vladimir eBrusic Vladimir eBrusic Seung Jo eKim Ellis L Reinherz Ellis L Reinherz |
| author_facet | Derin B Keskin Derin B Keskin Bruce eReinhold Bruce eReinhold Sun Young eLee Guanglan eZhang Guanglan eZhang Simon eLank David eO'Connor Ross S Berkowitz Vladimir eBrusic Vladimir eBrusic Seung Jo eKim Ellis L Reinherz Ellis L Reinherz |
| author_sort | Derin B Keskin |
| collection | DOAJ |
| description | Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711-19 peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E711-19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711-19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711-19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development. |
| first_indexed | 2024-04-12T00:07:01Z |
| format | Article |
| id | doaj.art-429b57706f1b45fa98a65a904b602c7b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T00:07:01Z |
| publishDate | 2011-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-429b57706f1b45fa98a65a904b602c7b2022-12-22T03:56:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-12-01210.3389/fimmu.2011.0007517277Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimensDerin B Keskin0Derin B Keskin1Bruce eReinhold2Bruce eReinhold3Sun Young eLee4Guanglan eZhang5Guanglan eZhang6Simon eLank7David eO'Connor8Ross S Berkowitz9Vladimir eBrusic10Vladimir eBrusic11Seung Jo eKim12Ellis L Reinherz13Ellis L Reinherz14Dana-Farber Cancer InstituteHarvard Medical SchoolDana-Farber Cancer InstituteHarvard Medical SchoolCHA UniversityDana-Farber Cancer InstituteHarvard Medical SchoolUniversity of Wisconsin-MadisonUniversity of Wisconsin-MadisonBrigham and Women's HospitalDana-Farber Cancer InstituteHarvard Medical SchoolCHA UniversityDana-Farber Cancer InstituteHarvard Medical SchoolPersistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711-19 peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E711-19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711-19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711-19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00075/fullMass SpectrometryHuman Papilloma VirusTumor antigensCTL targetsE7GILT |
| spellingShingle | Derin B Keskin Derin B Keskin Bruce eReinhold Bruce eReinhold Sun Young eLee Guanglan eZhang Guanglan eZhang Simon eLank David eO'Connor Ross S Berkowitz Vladimir eBrusic Vladimir eBrusic Seung Jo eKim Ellis L Reinherz Ellis L Reinherz Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens Frontiers in Immunology Mass Spectrometry Human Papilloma Virus Tumor antigens CTL targets E7 GILT |
| title | Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens |
| title_full | Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens |
| title_fullStr | Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens |
| title_full_unstemmed | Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens |
| title_short | Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens |
| title_sort | direct identification of an hpv 16 tumor antigen from cervical cancer biopsy specimens |
| topic | Mass Spectrometry Human Papilloma Virus Tumor antigens CTL targets E7 GILT |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00075/full |
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