A new strategy for tumor antigen discovery based on in vitro priming of naive T cells with dendritic cells
| Autor: | H, Kao, A A, Amoscato, P, Ciborowski, O J, Finn |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
Spectrometry Mass Electrospray Ionization Dose-Response Relationship Drug Macrophages T-Lymphocytes Genes MHC Class I Dendritic Cells CD8-Positive T-Lymphocytes Mass Spectrometry Mice Antigens Neoplasm HLA Antigens Tumor Cells Cultured Animals Humans Electrophoresis Polyacrylamide Gel Peptides Cell Division Cells Cultured Chromatography High Pressure Liquid Signal Transduction Subcellular Fractions |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 7 |
| ISSN: | 1078-0432 |
| Popis: | We describe a method for discovery of new tumor antigens that uses dendritic cells (DCs) as antigen-presenting cells to prime autologous naive CD4+ and CD8+ T cells from healthy donors against tumor proteins and peptides. For the identification of HLA class I-restricted tumor antigens, peptides were extracted from tumor HLA class I molecules, fractionated by reverse phase-high performance liquid chromatography, and loaded onto in vitro-generated DCs to prime naïve CD8+ T cells. Our results show that we were able to prime naive CD8+ T cells in vitro to several peptide fractions and generate specificity for the tumor. Electrospray ionization mass spectrometry was used to confirm that these fractions contained peptides derived from MHC class I molecules, and the primed CD8+ T cells were used to further analyze the immunostimulatory peptide fractions. For the identification of HLA class II-restricted tumor antigens, we fractionated tumor protein extracts using reverse phase-high performance liquid chromatography and loaded individual fractions onto DCs to prime naive CD4+ T cells. Our results show that we were also able to prime naive CD4+ T cells to several protein fractions and generate specificity for the tumor. These results illustrate the potential of this method to identify new immunostimulatory MHC class I- and class II-restricted tumor antigens. |
| Databáze: | OpenAIRE |
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