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 QM_α and DM_β 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 QM_α and DM_β 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.

2 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), DM_β (center), or QM_α (right). (rForce indicates relative force.)

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