CD83 Is a Sialic Acid-Binding Ig-Like Lectin (Siglec) Adhesion Receptor that Binds Monocytes and a Subset of Activated CD8+ T Cells

Abstract

To help determine CD83 function, a cDNA encoding a soluble protein containing the CD83 extracellular domain was fused with a mutated human IgG1 constant region (CD83Ig) and expressed by stable transfection of Chinese hamster ovary cells. Purified CD83Ig bound to peripheral blood monocytes and a subset of activated CD3+CD8+ lymphocytes but did not bind to FcR. Monocytes that had adhered to plastic lost their ability to bind to CD83Ig after 90 min of in vitro incubation. CD83Ig bound to two of five T cell lines tested, HPB-ALL and Jurkat. The binding to HPB-ALL cells significantly increased when they were grown at a low pH (pH 6.5), whereas binding to Jurkat cells increased after apoptosis was induced with anti-Fas mAb. B cell and monocytic lines did not bind CD83Ig and neither did CD56+ NK cells or granulocytes. Full-length CD83 expressed by a transfected carcinoma line mediated CD83-dependent adhesion to HPB-ALL cells. CD83Ig immunoprecipitated and immunoblotted a 72-kDa protein from HPB-ALL cells. Binding of CD83Ig to HPB-ALL cells was eliminated by neuraminidase treatment of the cells. We conclude that CD83 is an adhesion receptor with a counterreceptor expressed on monocytes and a subset of activated or stressed T lymphocytes, and that interaction between CD83 and its counterreceptor is dependent upon the state of glycosylation of a 72-kDa counterreceptor by sialic acid residues. In view of the selectivity of the expression of CD83 and its ligand, we postulate that the interaction between the two plays an important role in the induction and regulation of immune responses.

Dendritic cell CD83: A therapeutic target or innocent bystander?

“…Recent studies have therefore focused on CD83 as a potential target for therapeutic intervention, with a flurry of exciting, yet often contradictory papers providing new insight into the potential of this target for a variety of applications [2]. In this issue, Pashine et al demonstrate that the picture may be more complex [3], with conclusions that differ from those of previous publications [4][5][6][7][8][9][10][11]. Unfortunately, regulating immune responses and autoimmune disease is rarely simple, and offers both therapeutic opportunities and traps that must be carefully explored before pursuit.…”

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

“…CD83 is a cell surface membrane glycoprotein whose surface expression is largely restricted to DCs (55). The precise functions of this molecule remain unknown (76,77), but CD83 may serve important roles during intercellular interactions (77)(78)(79), as membrane-bound CD83 increases the stimulatory capacity of DCs (79). Further, previous studies suggest that CD83 mediates adhesion to monocytes and CD8 ϩ T cells (80).…”

CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells

“…Cell-surface or immobilized CD83 has been shown to enhance CD8 + T cell activation [12]. The release of soluble CD83 from activated B cells and DCs, and the ability of soluble CD83 to bind to activated CD8 + T cells, monocytes and DCs, may represent another mechanism through which CD83 regulates antigen presentation and T cell proliferation or differentiation [12,[16][17][18]. Human cytomegalovirus appears to exploit this mechanism to evade host immunity [18].…”

“…Immobilized CD83 was shown to promote the activation of CD8 T cells in peripheral blood mononuclear cells through monocytes [12]. It also binds to activated CD8 + T cells, although it is not clear whether sialic acid residues on the T cells are involved [16]. Soluble CD83 was also shown to bind to DCs, and the binding was shown to inhibit DC maturation and immunostimulation [17].…”

“…Both B cells and DCs release soluble CD83 upon activation [13,14]. Like siglecs (sialicacid-binding, immunoglobulin-like lectins), the soluble form of CD83 binds to sialic acid residues on a 72 kDa monocyte surface protein [15,16], but it lacks the inhibitory motif found in the cytoplasmic domains of some siglecs [15]. Immobilized CD83 was shown to promote the activation of CD8 T cells in peripheral blood mononuclear cells through monocytes [12].…”