CD84 Functions as a Homophilic Adhesion Molecule and Enhances IFN-γ Secretion: Adhesion Is Mediated by Ig-Like Domain 1

Abstract

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-γ secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.

Homophilic interaction of NTBA, a member of the CD2 molecular family: induction of cytotoxicity and cytokine release in human NK cells

“…According to this concept, the known ligands of the CD2-related proteins are represented by one or another member of this molecular family. In particular, it has been shown that these molecular interactions are either heterophilic, such as CD2/CD58, CD2/CD48, and CD244/ CD48, or homophilic, such as CD150/CD150, CD84/ CD84, and CS1/CS1 [22][23][24][25][26][27][28].…”

“…Both heterophilic and homophilic interactions have been described between different members of the CD2 family [22][23][24][25][26][27][28]. We therefore explored the possibility that NTBA may recognize one or another member of this family.…”

“…Different heterophilic or homophilic receptor/ligand interactions have been reported to occur between other members of the CD2 family. In particular, human CD2 binds CD58 [24], but it also binds with low affinity CD48 [25], whereas CD150 [26], CD84 [27], and CS1 [28] mediate homophilic interactions. In this study, using a soluble NTBA molecule we demonstrate that also NTBA recognizes itself.…”

Differential expression of CD150 (SLAM) family receptors by human hematopoietic stem and progenitor cells

“…The following biotinylated anti-human mAbs were produced in our laboratory: CD84 (CD84.1.21), CD150 (SLAM.4), CD229 (HLy9.1.84) and CD244 (2B4.69) [9][10][11][12]. Biotinylated anti-human CD48 (99A) was provided by R. Vilella (Hospital Clinic, Barcelona, Spain) and CD150 mAbs (clones A12, 1B12, 10F5, 11G2, and 5G4) by Cox Terhorst (Harvard Medical School, Cambridge, MA, USA).…”

Large-scale screening for novel low-affinity extracellular protein interactions

“…These cDNAs were cloned from either existing MGC clones or amplified from mixed-tissue human cDNA essentially as described (Collins et al 2004). Within this set of proteins are published negative interactions (Martin et al 2001;Kumaresan et al 2002;Falco et al 2004;Flaig et al 2004;Romero et al 2005), outlined with black circles in Figure 1D.…”