Induction, binding specificity and function of human ICOS

K C Beier1, A Hutloff, A M Dittrich

  • 1Molecular Immunology, Robert Koch-Institute, Berlin, Germany.

Insights

Inducible co-stimulator (ICOS) is a T cell molecule crucial for immune responses. ICOS enhances cytokine production and prevents T cell death, playing a key role in immune regulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The inducible co-stimulator (ICOS) is a T cell-specific surface molecule related to CD28 and CTLA-4.
  • ICOS plays a role in T cell activation and immune responses.

Purpose of the Study:

  • To characterize the human inducible co-stimulator (ICOS) molecule.
  • To investigate the induction, function, and expression of ICOS in T cells.

Main Methods:

  • Analysis of human ICOS protein structure and glycosylation.
  • Investigation of ICOS induction by phorbol 12-myristate 13-acetate, ionomycin, and Cyclosporin A.
  • Examination of ICOS expression during T cell activation and in various lymphoid tissues.

Main Results:

  • Human ICOS is a 55-60 kDa homodimer with distinct subunits.
  • ICOS is upregulated early in T cell activation, independent of the CD40 ligand/CD40 pathway but dependent on CD28/B7.
  • ICOS co-stimulates various cytokines (IL-4, IL-5, IL-6, IFN-γ, TNF-α, GM-CSF, IL-10) and prevents T cell apoptosis.

Conclusions:

  • ICOS is a critical co-stimulatory molecule involved in T cell activation, cytokine production, and survival.
  • ICOS expression is regulated by T cell activation signals and found in specific immune microenvironments.
  • The findings highlight ICOS as a potential therapeutic target in immune modulation.

Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
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.
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...