MHC class I-presented lung cancer-associated tumor antigens identified by immunoproteomics analysis are targets for cancer-specific T cell response

Vivekananda Shetty, Gomathinayagam Sinnathamby, Zacharie Nickens, Punit Shah, Julie Hafner, Lisa Mariello, Shivali Kamal, Gordana Vlahovic', H. Kim Lyerly, Michael A. Morse, Ramila Philip

Research output: Contribution to journalArticlepeer-review

Abstract

The development of potent cancer vaccines for common malignancies such as lung cancer requires identification of suitable target antigens. We hypothesized that peptide epitopes naturally presented by MHC class I molecules on the surface of cancer cells would be the most relevant targets. We used LC/MS/MS analysis and identified 68 MHC class I-presented peptides from lung cancer cells. Using the criteria of strong consensus for HLA-A2 binding and relevance of the source proteins to malignant phenotype, we selected 8 peptides for functional characterization. These peptides, with a range of binding affinities, were confirmed to stabilize HLA-A2 molecules and were used to activate peptide-specific CTLs that efficiently recognized lung tumor cells. No correlation between the transcript levels of the source proteins and the extent of peptide-specific T cell recognition of lung cancer cells was observed. Furthermore, the peptide specific CTLs failed to recognize HLA-A2+ normal lung cells despite expression of the mRNA encoding the source proteins from which the peptides were derived. We conclude that MHC class I associated peptide epitopes are a more relevant source of authentic tumor antigens than over-expressed proteins and the identified peptides may be used as antigens for therapeutic vaccine strategies to treat lung cancer.

Original languageEnglish (US)
Pages (from-to)728-743
Number of pages16
JournalJournal of Proteomics
Volume74
Issue number5
DOIs
StatePublished - May 1 2011

Keywords

  • Epitopes
  • Immunoproteomics
  • Immunotherapy
  • Lung cancer
  • Mass spectrometry
  • QRT-PCR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Fingerprint Dive into the research topics of 'MHC class I-presented lung cancer-associated tumor antigens identified by immunoproteomics analysis are targets for cancer-specific T cell response'. Together they form a unique fingerprint.

Cite this