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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ioannidou K,Baumgaertner P,Gannon PO,Speiser MF,Allard M,Hebeisen M,Rufer N,Speiser DE

doi

10.1038/srep44320

subject

Has Abstract

pub_date

2017-03-13 00:00:00

pages

44320

issn

2045-2322

pii

srep44320

journal_volume

7

pub_type

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