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AI-driven computational methods and benchmarking for T-cell antigen identification - PubMed

5 hours ago
  • #AI in immunology
  • #mRNA vaccines
  • #T-cell antigen identification
  • The rise of mRNA vaccines underscores the importance of T-cell antigen identification in vaccinology and personalized medicine.
  • T-cell recognition involves a ternary interaction between TCR, MHC molecule, and peptide antigen (pMHC complex).
  • AI-driven computational methods are crucial for predicting TCR-pMHC binding.
  • The review categorizes methods for MHC-I, MHC-II, and TCR-pMHC binding prediction and evaluates foundational data resources.
  • A benchmarking study of 18 TCR-pMHC prediction models reveals a significant generalization gap under out-of-distribution (OOD) conditions.
  • Current models show marginal predictive gains when faced with novel epitope variants.
  • The study highlights the need for improved structural modeling, multi-omics data integration, and generative models for de novo TCR design.
  • Advancing these computational methods could transition immunoinformatics from prediction to rational design.