A functionally validated TCR-pMHC database for TCR specificity model development.

ABSTRACT: Accurate prediction of TCR specificity forms a holy grail in immunology and large language models and computational structure predictions provide a path to achieve this. Importantly, current TCR-pMHC prediction models have been trained and evaluated using historical data of unknown quality. Here, we develop and utilize a high-throughput synthetic platform for TCR assembly and evaluation to assess a large fraction of VDJdb-deposited TCR-pMHC entries using a standardized readout of TCR function. Strikingly, this analysis demonstrates that claimed TCR reactivity is only confirmed for 50% of evaluated entries. Intriguingly, the use of TCRbridge to analyze AlphaFold3 confidence metrics reveals a substantial performance in distinguishing functionally validating and non-validating TCRs even thoug

SUBMITTER: Messemaker M 

PROVIDER: S-EPMC12132471 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature