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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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Cells of the Adaptive Immune Response01:23

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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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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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Special Features of Adaptive Immunity01:20

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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.
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B Cell Activation and Differentiation01:24

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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.
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Immunological memory, a pivotal pillar of the adaptive immune system, is responsible for the body's ability to remember and respond more swiftly and effectively to previously encountered pathogens. This remarkable feature is what makes vaccines so effective in preventing diseases.
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Proper development of long-lived memory CD4 T cells requires HLA-DO function.

Nianbin Song1, Robin A Welsh1, Scheherazade Sadegh-Nasseri1

  • 1Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.

Frontiers in Immunology
|November 1, 2023
PubMed
Summary

The absence of HLA-DO (DO) impairs memory CD4 T cell development when encountering DM-resistant antigens, highlighting DO's role in immune memory. This finding offers new strategies for vaccine design to improve immune memory responses.

Keywords:
CD4 memory cellHLA-DOantigen processing and presentationmemory T cell developmentmemory T cell maintenance

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Area of Science:

  • Immunology
  • Molecular Biology
  • Vaccinology

Background:

  • HLA-DO (DO) is an accessory protein involved in peptide editing and antigen presentation.
  • DO influences the binding of peptides to HLA-DR1 molecules, with differential effects based on peptide sequence.
  • Antigen presentation by B cells during infection contraction phase is crucial for CD4 T cell memory development.

Purpose of the Study:

  • To investigate the role of DO in the development of memory CD4 T cells and B cells.
  • To determine how DO deficiency affects immune memory responses to antigens with differing peptide characteristics (DM-resistant vs. DM-sensitive).

Main Methods:

  • Utilized two model antigens: H5N1-Flu (DM-resistant) and OVA (DM-sensitive).
  • Employed DO-deficient transgenic (DO-KO) mice and wild-type (DO-WT) littermates.
  • Tracked memory CD4 T cell and B cell development using Tetramer staining and antibody markers.

Main Results:

  • DR1+DO-KO mice immunized with DM-resistant H5N1-Flu showed reduced CD4 memory T cells and memory B cells, with compromised recall responses compared to DR1+DO-WT mice.
  • Conversely, OVA-specific memory responses in DR1+DO-KO mice immunized with HA were normal, indicating antigen-specific effects.

Conclusions:

  • Absence of DO alters antigen presentation, impacting memory cell development, particularly for DM-resistant epitopes.
  • These findings provide novel insights for designing vaccines to enhance immune memory responses.