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Related Concept Videos

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...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
T Cell Types and Functions01:24

T Cell Types and Functions

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

Cytotoxic T Cells-mediated Immune Response

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...
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...

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Real-time Live Imaging of T-cell Signaling Complex Formation
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ICAM-1-dependent homotypic aggregates regulate CD8 T cell effector function and differentiation during T cell

Nicholas A Zumwalde1, Eisuke Domae, Matthew F Mescher

  • 1Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455.

Journal of Immunology (Baltimore, Md. : 1950)
|September 3, 2013
PubMed
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T cell clustering, mediated by ICAM-1 and LFA-1, regulates CD8 T cell effector function and differentiation. Blocking this clustering enhances cytotoxicity but promotes short-lived effector cells, suggesting a critical role in immune response balance.

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Area of Science:

  • Immunology
  • Cellular Biology
  • T cell activation

Background:

  • T cell activation involves homotypic T cell clustering via LFA-1/ICAM-1 interactions.
  • The functional role of T cell clustering in regulating T cell function is largely unknown.

Purpose of the Study:

  • To investigate the functional significance of T cell clustering in CD8 T cell activation and effector function.
  • To elucidate the role of ICAM-1 in T cell aggregation and its impact on immune responses.

Main Methods:

  • Utilized an APC-free in vitro system for activating purified naive CD8 T cells.
  • Employed ICAM-1-deficient CD8 T cells and anti-LFA-1 antibody to block T cell clustering.
  • Analyzed T cell proliferation, aggregation, cytokine production (IFN-γ), cytotoxicity, and receptor expression (CTLA-4, eomesodermin).

Main Results:

  • ICAM-1-deficient CD8 T cells failed to aggregate but showed normal proliferation, increased IFN-γ and granzyme B, and enhanced cytotoxicity.
  • Blocking LFA-1/ICAM-1 interactions mimicked the effects of ICAM-1 deficiency, reducing T cell clustering and increasing effector functions.
  • T cell clustering was found to limit antigen exposure, upregulate CTLA-4, downregulate eomesodermin, and promote a less differentiated effector phenotype in vivo.

Conclusions:

  • T cell clustering, mediated by ICAM-1/LFA-1, is a crucial regulator of CD8 T cell effector function and differentiation.
  • While clustering limits effector function, it may contribute to sustained T cell proliferation and a balanced immune response.
  • Understanding T cell clustering mechanisms offers insights into controlling immune responses and developing targeted therapies.