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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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...
Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
T Cell Types and Functions01:24

T Cell Types and Functions

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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

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Related Experiment Video

Updated: May 11, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

T-cell receptor specificity maintained by altered thermodynamics.

Florian Madura1, Pierre J Rizkallah, Kim M Miles

  • 1Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.

The Journal of Biological Chemistry
|May 24, 2013
PubMed
Summary
This summary is machine-generated.

Researchers engineered a T-cell receptor (TCR) with significantly enhanced binding affinity to major histocompatibility complex (MHC) molecules. This improved TCR maintains exquisite peptide specificity, revealing key molecular mechanisms of T-cell recognition.

Keywords:
Crystal StructureHigh Affinity T Cell Receptor (TCR)MelanomaPeptide-major Histocompatibility Complex (pMHC)Surface Plasmon Resonance (SPR)T-cellT-cell Receptor

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Generation of Human Alloantigen-specific T Cells from Peripheral Blood
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Generation of Human Alloantigen-specific T Cells from Peripheral Blood

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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

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Last Updated: May 11, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

Generation of Human Alloantigen-specific T Cells from Peripheral Blood
09:47

Generation of Human Alloantigen-specific T Cells from Peripheral Blood

Published on: November 21, 2014

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • T-cell receptors (TCRs) are crucial for adaptive immunity, recognizing peptide-MHC complexes on cell surfaces.
  • TCR-peptide-MHC interactions typically exhibit weak binding affinity, necessitating sensitive detection mechanisms.
  • Understanding the molecular basis of TCR peptide specificity is vital for developing targeted immunotherapies.

Purpose of the Study:

  • To explore the molecular mechanisms governing T-cell receptor (TCR) peptide specificity.
  • To investigate how enhanced binding affinity to major histocompatibility complex (MHC) molecules affects TCR specificity.
  • To characterize a melanoma-specific TCR with significantly improved binding affinity.

Main Methods:

  • Phage-display technology was employed to generate a high-affinity TCR variant (α24β17).
  • Binding affinity was quantified using dissociation constant (KD) measurements.
  • Thermodynamic analyses were performed to elucidate the role of solvation in specificity.

Main Results:

  • A melanoma-specific TCR (α24β17) was engineered with a 30,000-fold increase in binding affinity (KD = 0.6 nM).
  • Enhanced affinity was primarily achieved through novel TCR-MHC contacts.
  • Despite increased affinity, the engineered TCR retained high sensitivity to peptide backbone modifications, mirroring wild-type specificity.

Conclusions:

  • Engineered TCRs can achieve high affinity while preserving critical peptide specificity.
  • Solvation plays a significant role in dictating the exquisite peptide specificity of TCR recognition.
  • These findings provide insights into TCR-ligand interactions and inform the design of TCR-based therapeutics.