Heterogeneity assessment of functional T cell avidity
Autor: | Kalliopi Ioannidou, Petra Baumgaertner, Nathalie Rufer, Michel F. Speiser, Michael Hebeisen, Daniel E. Speiser, Philippe O. Gannon, Mathilde Allard |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Enzyme-Linked Immunospot Assay Cell Survival T cell Epitopes T-Lymphocyte chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Lymphocyte Activation Article Interferon-gamma 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Humans Cytotoxic T cell Avidity Immunity Cellular Multidisciplinary biology Chemistry ELISPOT Reproducibility of Results Clone Cells 030104 developmental biology medicine.anatomical_structure Polyclonal antibodies Monoclonal Immunology CD8-Positive T-Lymphocytes/cytology CD8-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/metabolism Cell Survival/immunology Clone Cells/immunology Clone Cells/metabolism Enzyme-Linked Immunospot Assay/methods Epitopes T-Lymphocyte/immunology Feasibility Studies Immunity Cellular/immunology Interferon-gamma/immunology Interferon-gamma/metabolism Lymphocyte Activation/immunology biology.protein 030215 immunology |
Zdroj: | Scientific reports, vol. 7, pp. 44320 Scientific Reports |
Popis: | The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation. |
Databáze: | OpenAIRE |
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