CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells

Cheryl E. Myers, Paul Hanavan, Kwasi Antwi, Daruka Mahadevan, A. Jamal Nadeem, Laurence Cooke, Adrienne C. Scheck, Zachary Laughrey, Douglas F. Lake

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Genetic instability of tumor cells can result in translation of proteins that are out of frame, resulting in expression of neopeptides. These neopeptides are not selfproteins and therefore should be immunogenic. By eluting peptides from human glioblastoma multiforme (GBM) tumor cell surfaces and subjecting them to tandem mass spectrometry, we identified a novel peptide (KLWGL TPKVTPS) corresponding to a frameshift in the 3′ betahydroxysteroid dehydrogenase type 7 (HSD3B7) gene. HLA-binding algorithms predicted that a 9-amino acid sequence embedded in this peptide would bind to HLAA* 0201. We confirmed this prediction using an HLAA* 0201 refolding assay followed by live cell relative affinity assays, but also showed that the 12-mer binds to HLA-A*0201. Based on the 9-mer sequence, optimized peptide ligands (OPL) were designed and tested for their affinities to HLA-A*0201 and their abilities to elicit antipeptide and CTL capable of killing GBM in vitro. Wildtype peptides as well as OPL induced anti-peptide CTL as measured by IFN-γ ELISPOTS. These CTL also killed GBM tumor cells in chromium-51 release assays. This study reports a new CTL target in GBM and further substantiates the concept that rational design and testing of multiple peptides for the same T-cell epitope elicits a broader response among different individuals than single peptide immunization.

Original languageEnglish (US)
Pages (from-to)1319-1332
Number of pages14
JournalCancer Immunology, Immunotherapy
Volume60
Issue number9
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • Cytotoxic T lymphocytes
  • Glioblastoma multiforme
  • Optimized peptide ligand

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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  • Cite this

    Myers, C. E., Hanavan, P., Antwi, K., Mahadevan, D., Nadeem, A. J., Cooke, L., Scheck, A. C., Laughrey, Z., & Lake, D. F. (2011). CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells. Cancer Immunology, Immunotherapy, 60(9), 1319-1332. https://doi.org/10.1007/s00262-011-1032-4