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Related Concept Videos

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...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
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...
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,...
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...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview

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

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Structural basis for self-recognition by autoimmune T-cell receptors.

Yiyuan Yin1, Yili Li, Roy A Mariuzza

  • 1Department of Antibody Engineering, Genentech, South San Francisco, CA, USA.

Immunological Reviews
|October 11, 2012
PubMed
Summary

T-cell receptors (TCRs) binding to self-peptides are structurally distinct and less stable, contributing to autoimmune diseases. These structural insights help understand T-cell self-recognition and evasion of immune tolerance.

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09:47

Generation of Human Alloantigen-specific T Cells from Peripheral Blood

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Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Area of Science:

  • Immunology
  • Structural Biology
  • Autoimmunity

Background:

  • T-cell receptors (TCRs) are crucial for distinguishing foreign from self-antigens via peptide-MHC (pMHC) interactions.
  • Dysfunctional recognition of self-peptides by T cells can lead to autoimmune diseases.
  • Structural studies of TCR-pMHC complexes offer insights into self-recognition mechanisms.

Purpose of the Study:

  • To elucidate the structural basis of self-recognition by autoreactive T-cell receptors (TCRs).
  • To understand how structural alterations in TCR-pMHC complexes contribute to autoimmunity and evasion of negative selection.
  • To explore the role of TCR cross-reactivity in self-peptide recognition.

Main Methods:

  • Structural analysis of autoimmune TCR-pMHC complexes.
  • Comparison of structural features between autoimmune and anti-microbial TCR-pMHC complexes.
  • Investigation of TCR-pMHC complex stability and binding topologies.

Main Results:

  • Two categories of self-reactive TCRs identified: altered binding topology and canonical binding with ligand defects.
  • Autoimmune TCR-pMHC complexes exhibit reduced stability compared to anti-microbial complexes.
  • Structural insights into TCR cross-reactivity and its potential role in autoimmunity.

Conclusions:

  • Structural differences in TCR-pMHC complexes underlie self-recognition and autoimmune disease.
  • Reduced complex stability allows autoreactive T cells to evade negative selection but remain functional.
  • Further research aims to link structural findings to TCR signaling and immune synapse formation.