Improve the functional correlation of TCR T cells by replacing affinity with avidity

Part of: TCR T cells

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.

1 Panel of TCR-transduced T cells based on their affinity. WT (baseline), DMβ (medium affinity), and QMα (high affinity) were selected for the experiment.

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), DMβ (center), or QMα (right). (rForce indicates relative force.)

Data courtesy of Dr. Nathalie Rufer at the University of Lausanne
Read more:
Hebeisen et al. (2013) Front. Immunol.

Solutions

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