Improve the functional correlation of TCR T
cells by replacing affinity with avidity
This study aimed to screen a panel of affinity-tuned TCR T cells and find the most potent candidates.
T cells with high antigen-affinity TCRs are, in general, functionally superior to those with low antigen-affinity. However, upon breaching an optimum, T-cell functionality diminishes, and negative T-cell regulation increases. The researchers selected three TCR constructs based on their affinity to evaluate T-cell avidities upon interaction with a melanoma cell line (Figure 3).
NY-ESO-1 peptide pulsing on QMα and DMβ resulted in marked avidity enhancement compared with the non-pulsed conditions (Figure 4). In contrast to affinity measurements, the avidity data correlated with T-cell function, explaining the diminishing results observed among T cells with the highest affinities.
The reverse relationship between affinities and avidities of QMα and DMβ can explain reduced functionalities of high-affinity TCR T cells. This outcome suggests that avidity is a better predictor of TCR T-cell functionality compared with affinity.
3 Panel of TCR-transduced T cells based on their affinity. WT (baseline), DMβ (medium affinity), and QMα (high affinity) were selected for the experiment.
4 Avidity curves showing the proportion of bound TCR T cells to non-pulsed or peptide-pulsed Na8 melanoma cells at increasing acoustic forces. Each plot represents measurements performed on WT (left), DMβ (center), or QMα (right). (rForce indicates relative force.)
