Conditional generation of real antigen-specific T cell receptor sequences.

ABSTRACT: Despite recent advances in T cell receptor (TCR) engineering, designing functional TCRs against arbitrary targets remains challenging due to complex rules governing cross-reactivity and limited paired data. Here we present TCR-TRANSLATE, a sequence-to-sequence framework that adapts low-resource machine translation techniques to generate antigen-specific TCR sequences against unseen epitopes. By evaluating 12 model variants of the BART and T5 model architectures, we identified key factors affecting performance and utility, revealing discordances between these objectives. Our flagship model, TCRT5, outperforms existing approaches on computational benchmarks, prioritizing functionally relevant sequences at higher ranks. Most significantly, we experimentally validated a computationally designe

SUBMITTER: Karthikeyan D 

PROVIDER: S-EPMC12460172 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature