# tcrLM: a lightweight protein language model for predicting T cell receptor and epitope binding specificity

arXiv: https://arxiv.org/abs/2406.16995 · HTML: https://mlsanity.com/paper/2406.16995/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 47 references that are in the map.
- First posted on arXiv 24 Jun 2024.

## Builds on (most cited first, 7 of 7)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [Adversarial Training Methods for Semi-Supervised Text Classification](https://mlsanity.com/paper/1605.07725/) (2016)
- [Transformer Quality in Linear Time](https://mlsanity.com/paper/2202.10447/) (2022)
- [TITAN: T Cell Receptor Specificity Prediction with Bimodal Attention Networks](https://mlsanity.com/paper/2105.03323/) (2021)

## Abstract (arXiv)

The anti-cancer immune response relies on the bindings between T-cell receptors (TCRs) and antigens, which elicits adaptive immunity to eliminate tumor cells. This ability of the immune system to respond to novel various neoantigens arises from the immense diversity of TCR repository. However, TCR diversity poses a significant challenge on accurately predicting antigen-TCR bindings. In this study, we introduce a lightweight masked language model, termed tcrLM, to address this challenge. Our approach involves randomly masking segments of TCR sequences and training tcrLM to infer the masked segments, thereby enabling the extraction of expressive features from TCR sequences. To further enhance robustness, we incorporate virtual adversarial training into tcrLM. We construct the largest TCR CDR3 sequence set with more than 100 million distinct sequences, and pretrain tcrLM on these sequences. The pre-trained encoder is subsequently applied to predict TCR-antigen binding specificity. We evaluate model performance on three test datasets: independent, external, and COVID-19 test set. The results demonstrate that tcrLM not only surpasses existing TCR-antigen binding prediction methods, but also outperforms other mainstream protein language models. More interestingly, tcrLM effectively captures the biochemical properties and positional preference of amino acids within TCR sequences. Additionally, the predicted TCR-neoantigen binding scores indicates the immunotherapy responses and clinical outcomes in a melanoma cohort. These findings demonstrate the potential of tcrLM in predicting TCR-antigen binding specificity, with significant implications for advancing immunotherapy and personalized medicine.