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 1).
NY-ESO-1 peptide pulsing on QMα and DMβ resulted in marked avidity enhancement compared with the non-pulsed conditions (Figure 2). 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.