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 koff-rates. We then investigated how varying sizes and avidities of monoclonal subpopulations translate into global koff-rates. Global koff-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.
Original language | English |
---|---|
Pages (from-to) | 582-596 |
Number of pages | 15 |
Journal | European Journal of Immunology |
Volume | 52 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2022 |
Keywords
- Avidity
- T-cell population
- TCR
- k-rate