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 language | English (US) |
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Pages (from-to) | 728-743 |
Number of pages | 16 |
Journal | Journal of Proteomics |
Volume | 74 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2011 |
Externally published | Yes |
Keywords
- Epitopes
- Immunoproteomics
- Immunotherapy
- Lung cancer
- Mass spectrometry
- QRT-PCR
ASJC Scopus subject areas
- Biophysics
- Biochemistry