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 mo lecules. Its cytoplasmic tail binds to Src homology 2 domain-containing pro tein IA (signaling lymphocytic activation molecule-associated protein), a p rotein encoded by the X-linked lymphoproliferative disease gene. It is pref erentially expressed on B lymphocytes, monocytes, and platelets. We show th at 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 th e CD84 ligand, we generated a soluble Ig fusion protein containing the huma n CD84 extracellular domains (CD84-Ig). Because receptor-ligand interaction s occur between several members of this subfamily, we assayed CD84-Ig bindi ng with all members of the CD2 family. CD84-Ig bound to CD84-transfected ce lls, whereas no binding was detected with cells expressing other CD2 subfam ily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizin g epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-I g fusion protein to CD84-transfected cells and platelets. Data from CD84 do main human/mouse chimeras further revealed that only the first extracellula r domain of the molecule is involved in the ligand receptor recognition. Th e CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, c oncurrent 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.