Global k(off)-rates of polyclonal T-cell populations merge subclonal avidities and predict functionality
Lueckemeier P, Molter KL, Jarosch S, Huppertz P, Purcarea A, Effenberger MJP, Nauerth M, D'Ippolito E, Busch DH, Schober K (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Abstract
The avidity of TCRs for peptide-major histocompatibility complexes (pMHCs) is a governing factor in how T cells respond to antigen. TCR avidity is generally linked to T-cell functionality and there is growing evidence for distinct roles of low and high avidity T cells in different phases of immune responses. While physiological immune responses and many therapeutic T-cell products targeting infections or cancers consist of polyclonal T-cell populations with a wide range of individual avidities, the role of T-cell avidity is usually investigated only in monoclonal experimental settings. In this report, we induced polyclonal T-cell responses with a wide range of avidities toward a model epitope by altered peptide ligands, and benchmarked global avidity of physiological polyclonal populations by investigation of TCR-pMHC k(off)-rates. We then investigated how varying sizes and avidities of monoclonal subpopulations translate into global k(off)-rates. Global k(off)-rates integrate subclonal avidities in a predictably weighted manner and robustly correlate with the functionality of murine polyclonal T-cell populations in vitro and in vivo. Surveying the full avidity spectrum is essential to accurately assess polyclonal immune responses and inform the design of polyclonal T-cell therapeutics.
Authors with CRIS profile
Involved external institutions
Germany (DE)How to cite
APA:
Lueckemeier, P., Molter, K.L., Jarosch, S., Huppertz, P., Purcarea, A., Effenberger, M.J.P.,... Schober, K. (2022). Global k(off)-rates of polyclonal T-cell populations merge subclonal avidities and predict functionality. European Journal of Immunology. https://doi.org/10.1002/eji.202149597
MLA:
Lueckemeier, Philipp, et al. "Global k(off)-rates of polyclonal T-cell populations merge subclonal avidities and predict functionality." European Journal of Immunology (2022).
BibTeX: Download