# Enhancing TCR-Peptide Interaction Prediction with Pretrained Language Models and Molecular Representations

arXiv: https://arxiv.org/abs/2505.01433 · HTML: https://mlsanity.com/paper/2505.01433/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 5 of its 43 references that are in the map.
- First posted on arXiv 22 Apr 2025.

## Builds on (most cited first, 5 of 5)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Time-LLM: Time Series Forecasting by Reprogramming Large Language Models](https://mlsanity.com/paper/2310.01728/) (2023)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [TITAN: T Cell Receptor Specificity Prediction with Bimodal Attention Networks](https://mlsanity.com/paper/2105.03323/) (2021)

## Abstract (arXiv)

Understanding the binding specificity between T-cell receptors (TCRs) and peptide-major histocompatibility complexes (pMHCs) is central to immunotherapy and vaccine development. However, current predictive models struggle with generalization, especially in data-scarce settings and when faced with novel epitopes. We present LANTERN (Large lAnguage model-powered TCR-Enhanced Recognition Network), a deep learning framework that combines large-scale protein language models with chemical representations of peptides. By encoding TCR beta-chain sequences using ESM-1b and transforming peptide sequences into SMILES strings processed by MolFormer, LANTERN captures rich biological and chemical features critical for TCR-peptide recognition. Through extensive benchmarking against existing models such as ChemBERTa, TITAN, and NetTCR, LANTERN demonstrates superior performance, particularly in zero-shot and few-shot learning scenarios. Our model also benefits from a robust negative sampling strategy and shows significant clustering improvements via embedding analysis. These results highlight the potential of LANTERN to advance TCR-pMHC binding prediction and support the development of personalized immunotherapies.