Paul Thomas @pgtimmune.bsky.social · 04/09/2026Adding these close negative examples improved TCR specificity classification substantially in our tests. More broadly, the results argue that TCR recognition is a property of the paired receptor, not simply the sum of two independent chain scores. 110
Paul Thomas @pgtimmune.bsky.social · 04/09/2026Structure helped explain part of the story. More promiscuous fixed chains tended to make more predicted contacts with pMHC, leaving greater latitude for their partner chain. But even current structural models could not fully resolve all near identical binder and nonbinder pairs. 100
Paul Thomas @pgtimmune.bsky.social · 04/09/2026There is also a practical opportunity. Starting from a single TCR against a fibrolamellar carcinoma neoantigen, partner chain exchange identified additional neoantigen reactive TCRs with reduced or absent recognition of the corresponding self peptide. 120
