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CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1.

CD84 is a member of the CD2 subset of the Ig superfamily of cell surface molecules. Its cytoplasmic tail binds to Src homology 2 domain-containing protein 1A (signaling lymphocytic activation molecule-associated protein), a protein encoded by the X-linked lymphoproliferative disease gene. It is preferentially expressed on B lymphocytes, monocytes, and platelets. We show that it is also expressed on thymocytes and T cells. CD84 was positive on CD4-CD8- thymocytes, and its expression decreased with cell maturation. It is expressed on mature T cells preferentially on CD45RO+. To identify the CD84 ligand, we generated a soluble Ig fusion protein containing the human CD84 extracellular domains (CD84-Ig). Because receptor-ligand interactions occur between several members of this subfamily, we assayed CD84-Ig binding with all members of the CD2 family. CD84-Ig bound to CD84-transfected cells, whereas no binding was detected with cells expressing other CD2 subfamily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizing epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-Ig fusion protein to CD84-transfected cells and platelets. Data from CD84 domain human/mouse chimeras further revealed that only the first extracellular domain of the molecule is involved in the ligand receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, concurrent ligation of human CD84 with mAbs or CD84-Ig and CD3 enhanced IFN-gamma secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.

Pubmed ID: 11564780

Authors

  • Martin M
  • Romero X
  • de la Fuente MA
  • Tovar V
  • Zapater N
  • Esplugues E
  • Pizcueta P
  • Bosch J
  • Engel P

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

October 1, 2001

Associated Grants

None

Mesh Terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD
  • Binding, Competitive
  • COS Cells
  • Cell Adhesion
  • Cell Adhesion Molecules
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Humans
  • Immunoglobulins
  • Interferon-gamma
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Mice
  • Protein Structure, Tertiary
  • T-Lymphocytes
  • Thymus Gland
  • Tumor Cells, Cultured