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.
Martin
M
M
Immunology Unit, Department of Cellular Biology and Pathology, Medical School, Institut d'Investigacions Biomèdiques August Pi y Sunyer, C/Casanova 143, Barcelona E-08036, Spain.
Romero
X
X
de la Fuente
M A
MA
Tovar
V
V
Zapater
N
N
Esplugues
E
E
Pizcueta
P
P
Bosch
J
J
Engel
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D001667:Binding, Competitive; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D017434:Protein Structure, Tertiary; D000071176:Signaling Lymphocytic Activation Molecule Family; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C498970:CD84 protein, human; C498971:Cd84 protein, mouse; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C430423:LY9 protein, human; D008562:Membrane Glycoproteins; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma