Leukocyte function-associated antigen 1 (LFA-1) is a signaling molecule for cytoskeletal changes in a human T cell

D Kelleher1, A Murphy, D Cullen

  • 1Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Ireland.

Insights

Stimulating human T cells with LFA-1 antibodies causes dendritic processes containing cytoskeletal elements. This signaling molecule may reorganize the T cell cytoskeleton, an effect prolonged by phorbol myristate acetate.

Area of Science:

  • Immunology
  • Cell Biology
  • Cytoskeletal Dynamics

Background:

  • The HuT 78/2 clone is a human T cell line with an activated phenotype.
  • T cell activation and function involve complex cellular rearrangements.

Purpose of the Study:

  • To investigate the role of LFA-1 (lymphocyte function-associated antigen 1) in T cell morphology.
  • To explore the signaling pathways involved in T cell cytoskeletal reorganization.

Main Methods:

  • Stimulation of HuT 78/2 T cell clone with immobilized anti-LFA-1 antibody.
  • Microscopic analysis to observe cellular morphology and process formation.
  • Immunofluorescence staining to identify cytoskeletal components (microtubules, intermediate filaments).
  • Treatment with phorbol myristate acetate (PMA) to assess synergistic effects.

Main Results:

  • Immobilized anti-LFA-1 antibody induced the development of dendritic processes in the majority of HuT 78/2 cells.
  • These dendritic processes were found to contain cytoskeletal elements, including microtubules and intermediate filaments.
  • Phorbol myristate acetate (PMA) synergized with and prolonged the observed effect of LFA-1 stimulation.

Conclusions:

  • The LFA-1 molecule may act as a signaling molecule that triggers cytoskeletal reorganization in human T cells.
  • Cytoskeletal rearrangements are a key component of T cell activation and response.
  • Combined stimulation via LFA-1 and PMA enhances and sustains T cell morphological changes.

Related Concept Videos

Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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 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...
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...