title: Heterogeneity assessment of functional T cell avidity.
abstract: 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.
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Ioannidou
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.affiliation: Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Gannon
authors.affiliation: IBM Research - Zurich, Rueschlikon, Switzerland.
authors.forename: Michel F
authors.initials: MF
authors.lastname: Speiser
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Allard
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hebeisen
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.|Department of Oncology, Lausanne University Hospital Center (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D015203:Reproducibility of Results
chemical_list: D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma