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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.
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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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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.
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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.
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Generation of Human Alloantigen-specific T Cells from Peripheral Blood
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Original Antigenic Sin in CD4+ T Cells.

Mingran Zhang1, Junling Ma2, Meili Li3

  • 1College of Information Science and Technology, Donghua University, Shanghai, China.

Immunology
|March 8, 2025
PubMed
Summary
This summary is machine-generated.

Original antigenic sin (OAS) weakens immune responses to new infections. This study reveals that CD4+ T cell regulation, involving regulatory T cells (Tregs), drives OAS by suppressing naive T cell responses, impacting vaccine effectiveness.

Keywords:
IL‐2T cell proliferationTregsmathematical modelparameter estimation

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Area of Science:

  • Immunology
  • Computational Biology
  • Mathematical Modeling

Background:

  • Original antigenic sin (OAS) describes how prior antigen exposure impairs adaptive antibody responses to subsequent, different infections.
  • This phenomenon can reduce the efficacy of immunity from vaccines or prior infections.

Purpose of the Study:

  • To elucidate the mechanism by which CD4+ T cells contribute to original antigenic sin (OAS).
  • To investigate the role of regulatory T cells (Tregs) in T cell-mediated OAS.

Main Methods:

  • Developed a mathematical model simulating naive and memory CD4+ T cell proliferation, IL-2 dynamics, and Treg responses.
  • Calibrated the model with experimental data.
  • Performed numerical simulations to analyze T cell responses under varying antigen cross-reactivity.

Main Results:

  • Demonstrated that antigen-nonspecific CD4+ T cell proliferation and regulation signals drive OAS.
  • Showed that memory CD4+ T cells trigger Tregs, prematurely suppressing naive CD4+ T cell responses.
  • Found that immune response is weakest at intermediate antigen cross-reactivity, a hallmark of OAS.

Conclusions:

  • Antigen-nonspecific regulation by CD4+ T cells, mediated by Tregs, is a key mechanism underlying OAS.
  • This T cell-driven OAS mechanism may also explain the phenomenon observed in antibody responses.
  • Understanding this mechanism is crucial for improving vaccine design and predicting immune responses to infections.