Discrete diffusion model DTCR designs T-cell receptors for unseen immune targets

bravo_abad · x · 2026-08-27

Haoyan Wang and coauthors introduce DTCR, a discrete diffusion model that generates candidate T-cell receptors conditioned on a specific peptide–MHC target — designing receptors for immune targets it has never encountered.

The key idea: protein sequences aren't treated as arbitrary strings. The forward diffusion corrupts amino acids using a BLOSUM-based transition matrix derived from evolutionary substitution patterns, while the reverse process incorporates a TCR–epitope binding predictor to steer generation toward binding candidates. A notable showcase of generative AI for immunotherapy design.

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