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
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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