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Many biological processes are governed by protein-ligand interactions. One such example is the recognition of self and nonself cells by the immune system. This immune response process is regulated by the major histocompatibility complex…

Quantitative Methods · Quantitative Biology 2017-04-14 Yeeleng Scott Vang , Xiaohui Xie

The major histocompatibility complex (MHC) molecules, which bind peptides for presentation on the cell surface, play an important role in cell-mediated immunity. In light of developing databases and technologies over the years, significant…

Biomolecules · Quantitative Biology 2023-01-26 Ayşenaz Ezgi Ergin , Deniz Turgay Altılar

T-cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. An effective binding between T-cell receptors (TCRs) and pathogen-derived peptides presented on Major Histocompatibility Complexes (MHCs)…

Quantitative Methods · Quantitative Biology 2025-09-05 Gian Marco Visani , Michael N. Pun , Anastasia A. Minervina , Philip Bradley , Paul Thomas , Armita Nourmohammad

Major histocompatibility complex class two (MHC-II) molecules are trans-membrane proteins and key components of the cellular immune system. Upon recognition of foreign peptides expressed on the MHC-II binding groove, helper T cells mount an…

Quantitative Methods · Quantitative Biology 2017-12-05 A. M. Degoot , Faraimunashe Chirove , Wilfred Ndifon

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

Motivation: In silico methods for the prediction of antigenic peptides binding to MHC class I molecules play an increasingly important role in the identification of T-cell epitopes. Statistical and machine learning methods, in particular,…

Quantitative Methods · Quantitative Biology 2007-05-23 Laurent Jacob , Jean-Philippe Vert

T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes is a central component of adaptive immunity, with implications for vaccine design, cancer immunotherapy, and autoimmune disease. While recent advances in machine learning…

Quantitative Methods · Quantitative Biology 2026-03-09 Jiarui Li , Zixiang Yin , Zhengming Ding , Samuel J. Landry , Ramgopal R. Mettu

T cells monitor the health status of cells by identifying foreign peptides displayed on their surface. T-cell receptors (TCRs), which are protein complexes found on the surface of T cells, are able to bind to these peptides. This process is…

Quantitative Methods · Quantitative Biology 2023-03-07 Ziqi Chen , Martin Renqiang Min , Hongyu Guo , Chao Cheng , Trevor Clancy , Xia Ning

The binding affinity between the T-cell receptors (TCRs) and antigenic peptides mainly determines immunological recognition. It is not a trivial task that T cells identify the digital sequences of peptide amino acids by simply relying on…

Cell Behavior · Quantitative Biology 2024-02-14 Jin Xu , Junghyo Jo

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

Personalized vaccines and T-cell immunotherapies depend critically on identifying peptide-MHC class I (pMHC-I) interactions capable of eliciting potent immune responses. However, current benchmarks and models inherit biases present in…

Quantitative Methods · Quantitative Biology 2025-08-22 Sergio Mares , Ariel Espinoza Weinberger , Nilah M. Ioannidis

The major histocompatibility complex (MHC) class-I pathway supports the detection of cancer and viruses by the immune system. It presents parts of proteins (peptides) from inside a cell on its membrane surface enabling visiting immune cells…

Quantitative Methods · Quantitative Biology 2021-11-16 Hans-Christof Gasser , Georges Bedran , Bo Ren , David Goodlett , Javier Alfaro , Ajitha Rajan

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…

Quantitative Methods · Quantitative Biology 2025-12-29 Cong Qi , Hanzhang Fang , Siqi jiang , Tianxing Hu , Zhi Wei

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

Predicting peptide--major histocompatibility complex I (pMHC-I) binding affinity remains challenging due to extreme allelic diversity ($\sim$30,000 HLA alleles), severe data scarcity for most alleles, and noisy experimental measurements.…

Quantitative Methods · Quantitative Biology 2025-07-18 Sergio E. Mares , Ariel Espinoza Weinberger , Nilah M. Ioannidis

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

Recent advancements in immune sequencing and experimental techniques are generating extensive T cell receptor (TCR) repertoire data, enabling the development of models to predict TCR binding specificity. Despite the computational challenges…

Quantitative Methods · Quantitative Biology 2024-07-24 Anna Weber , Aurélien Pélissier , María Rodríguez Martínez

Human leukocyte antigen (HLA) is an important molecule family in the field of human immunity, which recognizes foreign threats and triggers immune responses by presenting peptides to T cells. In recent years, the synthesis of tumor vaccines…

Quantitative Methods · Quantitative Biology 2022-08-10 Meng Wang , Chuqi Lei , Jianxin Wang , Yaohang Li , Min Li

Computational drug discovery provides an efficient tool helping large scale lead molecules screening. One of the major tasks of lead discovery is identifying molecules with promising binding affinities towards a target, a protein in…

Biological Physics · Physics 2019-09-18 Liangzhen Zheng , Jingrong Fan , Yuguang Mu

An unsolved challenge in the development of antigen specific immunotherapies is determining the optimal antigens to target. Comprehension of antigen-MHC binding is paramount towards achieving this goal. Here, we present CASTELO, a combined…

Quantitative Methods · Quantitative Biology 2020-12-09 David Bell , Giacomo Domeniconi , Chih-Chieh Yang , Ruhong Zhou , Leili Zhang , Guojing Cong
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