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T cells are a critical component of the adaptive immune system, playing a role in infectious disease, autoimmunity, and cancer. T cell function is mediated by the T cell receptor (TCR) protein, a highly diverse receptor targeting specific…

Machine Learning · Computer Science 2026-03-31 Marco Garcia Noceda , Matthew T Noakes , Andrew FigPope , Daniel E Mattox , Bryan Howie , Harlan Robins

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical…

Antigen-specific T cells play an essential role in immunoregulation and diseases such as cancer. Characterizing the T cell receptor (TCR) sequences that encode T cell specificity is critical for elucidating the antigenic determinants of…

The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T cell maturation in the thymus.…

Identifying T-cell receptors (TCRs) that interact with antigenic peptides provides the technical basis for developing vaccines and immunotherapies. The emergent deep learning methods excel at learning antigen binding patterns from known…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Qianhui Xu , Ruichen Xia , Stan Z. Li

We study the prediction of T-cell response for specific given peptides, which could, among other applications, be a crucial step towards the development of personalized cancer vaccines. It is a challenging task due to limited, heterogeneous…

Cell Behavior · Quantitative Biology 2025-02-28 Josua Stadelmaier , Brandon Malone , Ralf Eggeling

Physicochemically informed biological sequence generation has the potential to accelerate computer-aided cellular therapy, yet current models fail to \emph{jointly} ensure novelty, diversity, and biophysical plausibility when designing…

Computational Engineering, Finance, and Science · Computer Science 2025-10-08 Jiahao Ma , Hongzong Li , Ye-Fan Hu , Jian-Dong Huang

Designing full-length, epitope-specific TCR {\alpha}\b{eta} remains challenging due to vast sequence space, data biases and incomplete modeling of immunogenetic constraints. We present LSMTCR, a scalable multi-architecture framework that…

Computational Engineering, Finance, and Science · Computer Science 2025-10-09 Ruihao Zhang , Xiao Liu

T cells are central to the adaptive immune response, capable of detecting pathogenic antigens while ignoring healthy tissues with remarkable specificity and sensitivity. Quantitatively understanding how T cell receptors (TCRs) discriminate…

Molecular Networks · Quantitative Biology 2025-11-25 François X. P. Bourassa , Sooraj Achar , Grégoire Altan-Bonnet , Paul François

T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes is fundamental to adaptive immunity and central to the development of T cell-based immunotherapies. While transformer-based models have shown promise in predicting TCR-pMHC…

Computational Engineering, Finance, and Science · Computer Science 2025-09-23 Jiarui Li , Zixiang Yin , Zhengming Ding , Samuel J. Landry , Ramgopal R. Mettu

With the rise of Transformers and Large Language Models (LLMs) in Chemistry and Biology, new avenues for the design and understanding of therapeutics have opened up to the scientific community. Protein sequences can be modeled as language…

Machine Learning · Computer Science 2023-11-01 Seongwon Kim , Parisa Mollaei , Akshay Antony , Rishikesh Magar , Amir Barati Farimani

The complex nature of tripartite peptide-MHC-TCR interactions is a critical yet underexplored area in immunogenicity prediction. Traditional studies on TCR-antigen binding have not fully addressed the complex dependencies in triad binding.…

Biomolecules · Quantitative Biology 2025-01-06 Jiahao Ma , Hongzong Li , Jian-Dong Huang , Ye-Fan Hu , Yifan Chen

Diverse T and B cell repertoires play an important role in mounting effective immune responses against a wide range of pathogens and malignant cells. The number of unique T and B cell clones is characterized by T and B cell receptors (TCRs…

Quantitative Methods · Quantitative Biology 2026-05-12 Lucas Böttcher , Sascha Wald , Tom Chou

It has been verified that only a small fraction of the neoantigens presented by MHC class I molecules on the cell surface can elicit T cells. The limitation can be attributed to the binding specificity of T cell receptor (TCR) to…

Quantitative Methods · Quantitative Biology 2022-06-24 Yiming Fang , Xuejun Liu , Hui Liu

B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively…

Populations and Evolution · Quantitative Biology 2023-12-22 Maria Francesca Abbate , Thomas Dupic , Emmanuelle Vigne , Melody A. Shahsavarian , Aleksandra M. Walczak , Thierry Mora

Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform…

T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a…

Populations and Evolution · Quantitative Biology 2018-03-23 Hanrong Chen , Arup K. Chakraborty , Mehran Kardar

The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented…

Populations and Evolution · Quantitative Biology 2021-02-05 Zachary Sethna , Giulio Isacchini , Thomas Dupic , Thierry Mora , Aleksandra M. Walczak , Yuval Elhanati

Cancer is a complex disease characterized by uncontrolled cell growth. T cell receptors (TCRs), crucial proteins in the immune system, play a key role in recognizing antigens, including those associated with cancer. Recent advancements in…

Machine Learning · Computer Science 2025-06-12 Taslim Murad , Prakash Chourasia , Sarwan Ali , Imdad Ullah Khan , Murray Patterson

Predicting how cells respond to genetic perturbations is fundamental to understanding gene function, disease mechanisms, and therapeutic development. While recent deep learning approaches have shown promise in modeling single-cell…

Machine Learning · Computer Science 2026-03-10 Andrea Giuseppe Di Francesco , Andrea Rubbi , Pietro Liò