CD83 Human
Description
Molecular Structure and Isoforms
CD83 exists in two primary forms:
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Membrane-bound CD83 (mCD83):
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Contains an extracellular V-type immunoglobulin (Ig)-like domain (residues 20–144), transmembrane region (145–166), and cytoplasmic tail (167–205) .
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Forms homotrimers stabilized by disulfide bonds involving five cysteine residues in the extracellular domain .
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Crystal structure (PDB: 5N2D) reveals a truncated Ig-like fold lacking typical β-strands C', C'', and D, with enhanced flexibility in this region .
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Soluble CD83 (sCD83):
Table 2: CD83 Expression in Human Immune Cells
| Cell Type | Surface CD83 | Cytoplasmic CD83 | sCD83 Secretion |
|---|---|---|---|
| Mature Dendritic Cells | High | Low | Low |
| Activated B Cells | Moderate | High | High |
| Activated T Cells | Transient | Moderate | Undetectable |
| Monocytes | Low | High | Moderate |
Membrane-Bound CD83
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Co-stimulation: Enhances T-cell proliferation and cytotoxic responses via homotypic/heterotypic interactions resembling B7 family proteins .
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Tolerance Modulation: CD83-deficient DCs exhibit hyperactive IL-12/IL-23 production, exacerbating Th17-driven autoimmunity in experimental encephalomyelitis .
Soluble CD83
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Immunosuppression:
Autoimmune Diseases
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sCD83 administration suppresses experimental autoimmune encephalomyelitis (EAE) by reducing CNS inflammation .
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CD83-deficient mice show aggravated EAE due to impaired Treg expansion .
Transplantation
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Anti-CD83 antibodies (e.g., 3C12C) deplete activated DCs, preventing graft-versus-host disease (GVHD) while preserving antiviral T-cell memory .
Cancer
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Hodgkin Lymphoma: Elevated serum sCD83 correlates with disease progression; anti-CD83 antibody-drug conjugates (e.g., 3C12C-MMAE) selectively kill CD83+ tumor cells .
Table 3: Key Research Findings
| Study Model | Intervention | Outcome | Source |
|---|---|---|---|
| EAE (Mice) | sCD83 injection | 70% reduction in paralysis | |
| GVHD (SCID Mice) | Anti-CD83 mAb | Prevention of acute GVHD | |
| Hodgkin Lymphoma | 3C12C-MMAE | Targeted cytotoxicity in vitro |
Outstanding Questions and Future Directions
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Ligand Identification: Structural similarities to B7 family proteins suggest undiscovered binding partners .
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sCD83 Isoforms: Natural sCD83’s exact sequence and glycosylation patterns remain uncharacterized .
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Species Differences: Murine CD83 lacks the extended extracellular domain and soluble isoforms found in humans, complicating translational studies .
Product Specs
Product Science Overview
CD83 exists in two primary forms:
- Membrane-bound CD83 (mCD83): This form is predominantly expressed on the surface of mature dendritic cells (DCs) and other activated immune cells. It consists of an extracellular V-type immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic signaling tail . Membrane-bound CD83 is known to form trimers.
- Soluble CD83 (sCD83): This form is found in the serum and consists of the immunoglobulin-like domain alone. Soluble CD83 can assemble into dodecameric complexes .
CD83 is involved in several critical functions within the immune system:
- Regulation of Dendritic Cells: Membrane-bound CD83 is highly and stably expressed by mature dendritic cells, where it regulates their maturation, activation, and homeostasis .
- Immune Modulation: Soluble CD83 has been reported to have an immunosuppressive function, which is particularly elevated in patients with autoimmune diseases and certain hematological malignancies .
- Stabilization of Immune Molecules: The transmembrane domain of membrane-bound CD83 stabilizes major histocompatibility complex (MHC) class II, costimulatory molecules, and CD28 in the membrane by antagonizing MARCH-family E3 ubiquitin ligases .
CD83 has emerged as a promising target for therapeutic interventions due to its role in immune regulation:
- Autoimmune Diseases: The immunosuppressive properties of soluble CD83 make it a potential therapeutic agent for treating autoimmune diseases .
- Graft-Versus-Host Disease (GVHD): Anti-CD83 specific antibodies have shown efficacy in pre-clinical models of GVHD by depleting CD83+ cells without significantly affecting viral or tumor-specific memory T-cell responses .
- Transplantation: CD83-based therapeutics could be used to prevent donor organ rejection by selectively suppressing undesirable immune responses while preserving beneficial responses against infections and cancer .
Recombinant human CD83 is synthesized as a type I transmembrane glycoprotein that contains a 125 amino acid extracellular region, a 22 amino acid transmembrane segment, and a 39 amino acid cytoplasmic domain . This recombinant form is used in research and therapeutic applications to study and harness the immune-modulating properties of CD83.
