CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells
Identifieur interne : 002584 ( Main/Exploration ); précédent : 002583; suivant : 002585CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells
Auteurs : Cheryl E. Myers [États-Unis] ; Paul Hanavan [États-Unis] ; Kwasi Antwi [États-Unis] ; Daruka Mahadevan [États-Unis] ; A. Jamal Nadeem [États-Unis] ; Laurence Cooke [États-Unis] ; Adrienne C. Scheck [États-Unis] ; Zachary Laughrey [États-Unis] ; Douglas F. Lake [États-Unis]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2011-09-01.
English descriptors
Abstract
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.
Url:
DOI: 10.1007/s00262-011-1032-4
Affiliations:
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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. 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Lake</name><name sortKey="Lake, Douglas F" sort="Lake, Douglas F" uniqKey="Lake D" first="Douglas F." last="Lake">Douglas F. Lake</name><name sortKey="Laughrey, Zachary" sort="Laughrey, Zachary" uniqKey="Laughrey Z" first="Zachary" last="Laughrey">Zachary Laughrey</name><name sortKey="Mahadevan, Daruka" sort="Mahadevan, Daruka" uniqKey="Mahadevan D" first="Daruka" last="Mahadevan">Daruka Mahadevan</name><name sortKey="Nadeem, A Jamal" sort="Nadeem, A Jamal" uniqKey="Nadeem A" first="A. Jamal" last="Nadeem">A. Jamal Nadeem</name><name sortKey="Scheck, Adrienne C" sort="Scheck, Adrienne C" uniqKey="Scheck A" first="Adrienne C." last="Scheck">Adrienne C. Scheck</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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