Production of NY-ESO-1 peptide/DRB1*08:03 tetramers and ex vivo detection of CD4 T-cell responses in vaccinated cancer patients.
Vaccine
; 32(8): 957-64, 2014 Feb 12.
Article
en En
| MEDLINE
| ID: mdl-24397899
We established CD4 T-cell clones, Mz-1B7, and Ue-21, which recognized the NY-ESO-1 121-138 peptide from peripheral blood mononuclear cells (PBMCs) of an esophageal cancer patient, E-2, immunized with an NY-ESO-1 protein and determined the NY-ESO-1 minimal epitopes. Minimal peptides recognized by Mz-1B7 and Ue-21 were NY-ESO-1 125-134 and 124-134, respectively, both in restriction to DRB1*08:03. Using a longer peptide, 122-135, and five other related peptides, including either of the minimal epitopes recognized by the CD4 T-cell clones, we investigated the free peptide/DR recognition on autologous EBV-B cells as APC and peptide/DR tetramer binding. The results showed a discrepancy between them. The tetramers with several peptides recognized by either Mz-1B7 or the Ue-21 CD4 T-cell clone did not bind to the respective clone. On the other hand, unexpected binding of the tetramer with the peptide not recognized by CD4 T-cells was observed. The clone Mz-1B7 did not recognize the free peptide 122-135 on APC, but the peptide 122-135/DRB1*08:03 tetramer bound to the TCR on those cells. The failure of tetramer production and the unexpected tetramer binding could be due to a subtly modified structure of the peptide/DR tetramer from the structure of the free peptide/DR molecule. We also demonstrated that the NY-ESO-1 123-135/DRB1*08:03 tetramer detected ex vivo CD4 T-cell responses in PBMCs from patients after NY-ESO-1 vaccination in immunomonitoring.
Palabras clave
APC; CD4 T-cell; CHP-NY-ESO-1; Fmoc; HD; MFI; MHC class II tetramer; N-(9-fluorenyl)-methoxycarbonyl; NY-ESO-1; OLP; PBMC; Tumor immunology; antigen-presenting cell; complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 whole protein; healthy donor; mean fluorescence intensity; overlapping peptide; peripheral blood mononuclear cell
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Vacunas contra el Cáncer
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Cadenas beta de HLA-DR
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Proteínas de la Membrana
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Antígenos de Neoplasias
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Vaccine
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Países Bajos