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Vaccine ; 28(32): 5338-46, 2010 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-20665979

RESUMO

Three novel NY-ESO-1 CD4 T cell epitopes were identified using PBMC obtained from patients who were vaccinated with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1). The restriction molecules were determined by antibody blocking and using various EBV-B cells with different HLA alleles as APC to present peptides to CD4 T cells. The minimal epitope peptides were determined using various N- and C-termini truncated peptides deduced from 18-mer overlapping peptides originally identified for recognition. Those epitopes were DRB1*0901-restricted NY-ESO-1 87-100, DQB1*0401-restricted NY-ESO-1 95-107 and DRB1*0803-restricted NY-ESO-1 124-134. CD4 T cells used to determine those epitope peptides recognized EBV-B cells or DC that were treated with recombinant NY-ESO-1 protein or NY-ESO-1-expressing tumor cell lysate, suggesting that the epitope peptides are naturally processed. These CD4 T cells showed a cytokine profile with Th1 characteristics. Furthermore, NY-ESO-1 87-100 peptide/HLA-DRB1*0901 tetramer staining was observed. Multiple Th1-type CD4 T cell responses are beneficial for inducing effective anti-tumor responses after NY-ESO-1 protein vaccination.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/metabolismo , Antígenos HLA-DR/metabolismo , Proteínas de Neoplasias/metabolismo , Sequência de Aminoácidos , Apresentação de Antígeno , Linfócitos T CD4-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Linhagem Celular , Epitopos de Linfócito T/imunologia , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Humanos , Epitopos Imunodominantes/imunologia , Epitopos Imunodominantes/metabolismo , Dados de Sequência Molecular , Proteínas de Neoplasias/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo
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