TCR specificity prediction: strong motif in one chain can still be nonbinding with wrong partner

iskander · x · 2026-09-04

A reshared research thread highlights a key issue in TCR specificity prediction: a TCR containing a strong antigen motif in one chain can still be nonbinding when paired with the wrong partner chain. Approaches that lean heavily on single-chain similarity therefore misclassify many close nonbinders as positives — with direct implications for immune repertoire analysis and TCR-antigen binding models.

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