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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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RACE - Rapid Amplification of cDNA Ends02:35

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Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Diversity of Antigen Receptors01:28

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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Related Experiment Video

Updated: Jun 26, 2025

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
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Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain

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RACER-m leverages structural features for sparse T cell specificity prediction.

Ailun Wang1,2, Xingcheng Lin3,4, Kevin Ng Chau1,2

  • 1Center for Theoretical Biological Physics, Northeastern University, Boston, MA, USA.

Science Advances
|May 15, 2024
PubMed
Summary
This summary is machine-generated.

Predicting T cell receptor (TCR) specificity is challenging due to vast sequence diversity. Our structural model, RACER-m, accurately predicts TCR-antigen interactions with less training data.

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Area of Science:

  • Immunology
  • Computational Biology
  • Structural Biology

Background:

  • Predicting T cell receptor (TCR) specificity against antigens is complex due to extensive sequence diversity and limited training data.
  • Existing models struggle to accurately predict MHC-allele-restricted TCR-peptide interactions, despite incorporating structural information.

Purpose of the Study:

  • To develop a coarse-grained structural model (RACER-m) for predicting TCR-antigen recognition.
  • To leverage biophysical information from TCR-antigen crystal structures to improve prediction accuracy and reduce data requirements.

Main Methods:

  • Developed RACER-m, a coarse-grained structural model incorporating biophysical insights from TCR-antigen crystal structures.
  • Utilized publicly available structural data for model training and validation.

Main Results:

  • Explicit inclusion of structural data significantly reduced the number of training examples needed.
  • The model demonstrated reliable predictions of TCR recognition specificity and sensitivity across various contexts.
  • RACER-m successfully identified point-mutant peptides affecting binding affinity, outperforming sequence-based methods.

Conclusions:

  • RACER-m offers a robust approach for predicting TCR-antigen interactions, overcoming limitations of sequence-based methods.
  • The model's reliance on structural information makes it broadly applicable to diverse TCR-peptide pairs.
  • This approach can aid in understanding TCR specificity and designing immunotherapies.