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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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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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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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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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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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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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BRD7 as key factor in PBAF complex assembly and CD8+ T cell differentiation.

Feng Huang1,2, Yingtong Lin1,3, Yidan Qiao1

  • 1Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

JCI Insight
|July 2, 2024
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BRD7 is crucial for CD8+ T cell differentiation into effector cells. Its deficiency impairs viral clearance, highlighting BRD7 and the PBAF complex as key targets for immune therapies.

Keywords:
Adaptive immunityImmunologyInfectious diseaseT cell development

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Area of Science:

  • Immunology
  • Molecular Biology
  • Chromatin Remodeling

Background:

  • Naive CD8+ T cells develop into cytotoxic effector cells to clear infections.
  • The role of chromatin remodeling in this differentiation is not well understood.

Purpose of the Study:

  • To investigate the function of BRD7, a polybromo-associated BAF complex (PBAF) component, in CD8+ T cell differentiation.
  • To elucidate the molecular mechanisms by which BRD7 regulates effector T cell maturation.

Main Methods:

  • Studied CD8+ T cell differentiation in response to influenza virus and lymphocytic choriomeningitis virus (LCMV) infection in BRD7-deficient models.
  • Analyzed the assembly and function of the PBAF complex in effector T cells.
  • Assessed gene expression changes, including Tbx21, and chromatin accessibility.

Main Results:

  • BRD7 deficiency severely impaired CD8+ T cell effector function and viral clearance.
  • BRD7 expression increased during differentiation, facilitating PBAF complex assembly.
  • PBAF complex, regulated by BRD7, enhanced chromatin accessibility at the Tbx21 locus, promoting effector T cell maturation.

Conclusions:

  • BRD7 and the PBAF complex are essential regulators of CD8+ T cell differentiation into functional effector cells.
  • This pathway is critical for effective viral clearance and host recovery.
  • BRD7 and PBAF represent promising targets for enhancing immune therapies.