Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens.

Frontiers in Immunology
Derin B KeskinEllis L Reinherz

Abstract

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 (MS(3)) 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. MS(3) analysis of HLA-A(*)02 immunoprecipitates detected E7(11-19) peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E7(11-19) negative and lacked the HLA-A(*)02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A(*)02 alleles. Thus, the conserved E7(11-19) 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 E7(11-19) and a peptide from a thioreductase impo...Continue Reading

Citations

Jul 22, 2014·BioMed Research International·Guang Lan ZhangVladimir Brusic
Mar 27, 2016·Briefings in Bioinformatics·Sandeep Kumar DhandaGajendra P S Raghava
Sep 23, 2014·Frontiers in Immunology·Ellis L ReinherzBruce Reinhold
Mar 8, 2017·International Journal of Cancer. Journal International Du Cancer·Damayanti Das GhoshSharmila Sengupta

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Methods Mentioned

BETA
biopsy
biopsies
flow cytometry
454 sequencing
PCR
genotyping
amplicon sequencing
immunoprecipitation
FACS
gene array

Software Mentioned

MAFFT
ExPASy
BLAT
MID

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