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CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like

M Martin1, X Romero, M A de la Fuente

  • 1Immunology Unit, Department of Cellular Biology and Pathology, Medical School, Institut d'Investigacions Biomèdiques August Pi y Sunyer, C/Casanova 143, Barcelona E-08036, Spain.

Journal of Immunology (Baltimore, Md. : 1950)
|September 21, 2001
PubMed

Insights

CD84 is its own ligand, binding to itself on immune cells. This interaction enhances T cell responses, suggesting CD84 acts as a costimulatory molecule in immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Interactions

Background:

  • CD84, a cell surface molecule in the Ig superfamily, is expressed on lymphocytes and platelets.
  • Its cytoplasmic tail interacts with SLAM-associated protein, linked to X-linked lymphoproliferative disease.
  • CD84 expression is observed on thymocytes and T cells, varying with maturation.

Purpose of the Study:

  • To identify the ligand for the CD84 molecule.
  • To investigate the binding characteristics and functional consequences of CD84 interactions.

Main Methods:

  • Generation of a soluble CD84-Ig fusion protein to probe ligand binding.
  • Assaying CD84-Ig binding against various CD2 family members and transfected cells.
  • Utilizing anti-CD84 monoclonal antibodies and human/mouse chimeras to map binding domains.
  • Assessing the impact of CD84 ligation on T cell activation and cytokine secretion.

Main Results:

  • CD84-Ig specifically bound to CD84-expressing cells, indicating CD84 is its own ligand.
  • Binding involved the first extracellular domain of CD84 and was independent of its cytoplasmic tail.
  • Concurrent CD84 and CD3 ligation enhanced IFN-gamma secretion in human lymphocytes.

Conclusions:

  • CD84 engages in homophilic binding, acting as its own receptor and ligand.
  • CD84 functions as a costimulatory molecule, enhancing T cell-mediated immune responses.
  • The extracellular domain 1 is critical for CD84-CD84 recognition.

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