CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells.
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| 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 self-proteins 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 (KLWGLTPKVTPS) corresponding to a frameshift in the 3' beta-hydroxysteroid dehydrogenase type 7 (HSD3B7) gene. HLA-binding algorithms predicted that a 9-amino acid sequence embedded in this peptide would bind to HLA-A*0201. We confirmed this prediction using an HLA-A*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 anti-peptide and CTL capable of killing GBM in vitro. Wild-type 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.
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| Authors | Cheryl E Myers, Paul Hanavan, Kwasi Antwi, Daruka Mahadevan, A Jamal Nadeem, Laurence Cooke, Adrienne C Scheck, Zachary Laughrey, Douglas F Lake |
| Journal | Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 60 Issue 9 Pg. 1319-32 (Sep 2011) ISSN: 1432-0851 [Electronic] Germany |
| PMID | 21626031 (Publication Type: Journal Article) |
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