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Related Concept Videos

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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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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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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Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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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...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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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...
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Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

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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,...
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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: Jul 1, 2025

Examination of Thymic Positive and Negative Selection by Flow Cytometry
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Structural basis for self-discrimination by neoantigen-specific TCRs.

John P Finnigan1,2,3,4, Jenna H Newman1,2,3, Yury Patskovsky5,6

  • 1Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, NY, USA.

Nature Communications
|March 8, 2024
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Tumor neoantigens (neoAgs) are recognized by T cell receptors (TCRs) to kill cancer cells. This study reveals how a specific mutation enhances neoAg presentation and TCR binding, improving anti-tumor immunity.

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Area of Science:

  • Immunology
  • Cancer Research
  • Structural Biology

Background:

  • T cell receptors (TCRs) recognize tumor neoantigens (neoAgs) presented by MHC class I (MHC-I) molecules for cancer cell killing.
  • Understanding the structural and cellular factors that control TCR recognition of neoAgs is crucial for cancer immunotherapy.

Purpose of the Study:

  • To investigate the molecular and structural determinants of TCR recognition for a model neoantigen derived from B16F10 melanoma.
  • To analyze the impact of a specific mutation on neoantigen presentation and TCR binding affinity.

Main Methods:

  • Multi-level analysis including cellular, molecular, and structural studies.
  • Characterization of a model neoantigen (H2-Db/Hsf2 p.K72N68-76) and its cognate TCR (47BE7).

Main Results:

  • The p.K72N mutation was found to enhance binding to H2-Db, improving cell surface presentation and stabilizing the TCR 47BE7 epitope.
  • TCR 47BE7 demonstrated high functional avidity and selectivity, recognizing native B16F10 cells despite low antigen density.
  • The binding interface of TCR 47BE7 was broad and stringent, contributing to its recognition capabilities.

Conclusions:

  • The study provides insights into the generation of neoantigens modified by anchor-residue mutations.
  • Molecular and structural investigations of neoantigens in various MHC-I contexts are valuable for understanding neoantigen immunogenicity.
  • Findings advance the comprehension of TCR-neoantigen interactions in anti-tumor immunity.