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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shetty, V; Sinnathamby, G; Nickens, Z; Shah, P; Hafner, J; Mariello, L; Kamal, S; Vlahović, G; Lyerly, HK; Morse, MA; Philip, R

Published Date

  • May 2011

Published In

Volume / Issue

  • 74 / 5

Start / End Page

  • 728 - 743

PubMed ID

  • 21362506

Pubmed Central ID

  • 21362506

Electronic International Standard Serial Number (EISSN)

  • 1876-7737

International Standard Serial Number (ISSN)

  • 1874-3919

Digital Object Identifier (DOI)

  • 10.1016/j.jprot.2011.02.020

Language

  • eng