CD84 - CD84 molecule |Elisa - Clia - Antibody - Protein

Background

CD84 is a surface glycoprotein that belongs to the Signaling Lymphocytic Activation Molecule (SLAM) family of receptors, which are part of the larger immunoglobulin superfamily (IgSF). It plays a significant role in the regulation of immune cell interactions, particularly in B and T lymphocytes, natural killer (NK) cells, and myeloid cells. CD84 is predominantly expressed in hematopoietic cells, where it mediates cell signaling processes related to immune regulation, cell adhesion, and inflammatory responses.

CD84 is encoded by the CD84 gene, which is located on chromosome 1q23. It is widely expressed on immune cells such as B cells, T cells, dendritic cells, and monocytes, with notable expression also found on platelets. This molecule is critical for maintaining the balance of immune responses, including both activation and inhibition of immune functions. Due to its regulatory functions, CD84 has attracted considerable attention in immunology, cancer research, and autoimmune disease studies.

Protein Structure

The CD84 protein is a type I transmembrane glycoprotein, meaning it has a single-pass transmembrane domain with an extracellular N-terminus and an intracellular C-terminus. The CD84 structure consists of the following major regions:

Extracellular Domain (ECD):

• The extracellular region of CD84 is composed of two immunoglobulin-like (Ig-like) domains that are responsible for its interactions with other immune receptors. This domain plays a pivotal role in mediating homophilic interactions (CD84 binding to CD84 on adjacent cells) as well as heterophilic interactions with other SLAM family receptors.
• The Ig-like domains are essential for CD84’s function in cell adhesion and signaling transduction. These domains contain several conserved motifs typical of the immunoglobulin superfamily, including disulfide bonds that stabilize the protein structure.
• The extracellular domain is glycosylated at specific asparagine residues, a modification that influences the stability and function of the protein.

Transmembrane Domain:

• CD84 contains a single transmembrane helix, which anchors it in the cell membrane and helps transmit signals from the extracellular domain to the intracellular signaling pathways.
• The transmembrane region allows CD84 to interact with other SLAM family members, facilitating the formation of signaling complexes within lipid rafts, specialized membrane microdomains.

Intracellular Domain (Cytoplasmic Tail):

• The cytoplasmic region of CD84 contains several tyrosine-based motifs, including immunoreceptor tyrosine-based switch motifs (ITSMs). These motifs are critical for downstream signaling and the recruitment of Src homology 2 (SH2)-domain-containing proteins such as SAP (SLAM-associated protein) and SH2D1A.
• Upon phosphorylation of the tyrosine residues within the ITSMs, CD84 can recruit signaling adaptors like SAP, which modulate immune cell responses by interacting with other intracellular signaling molecules.
• The cytoplasmic tail also mediates interactions with various kinases and phosphatases, which influence immune cell activation, differentiation, and function.

Classification and Subtypes

CD84 is a member of the SLAM family within the immunoglobulin superfamily (IgSF). The SLAM family includes several receptors such as SLAMF1 (CD150), SLAMF2 (CD48), SLAMF3 (Ly9), SLAMF5 (CD84), SLAMF6 (NTB-A), and others. These receptors share structural similarities and are involved in immune cell signaling.

Although CD84 does not have multiple subtypes, its ability to interact with different SLAM family receptors and its association with various intracellular signaling proteins give it functional diversity. CD84 forms homophilic interactions (binding to itself on adjacent cells), which is a common feature of SLAM family proteins. This self-binding capability allows CD84 to influence cell-cell adhesion and immune synapse formation.

Function and Biological Significance

CD84 plays a crucial role in the regulation of immune responses, particularly in lymphocyte activation, inhibition, and cellular adhesion. The primary functions of CD84 include:

Modulation of Immune Cell Activation:

• CD84 acts as both a positive and negative regulator of immune responses, depending on the context. By binding to other CD84 molecules or engaging with other SLAM family receptors, CD84 can modulate T cell and B cell activation.
• In T cells, CD84 interaction can lead to increased proliferation and cytokine production when paired with costimulatory signals. In contrast, under certain conditions, CD84 engagement may result in the attenuation of excessive immune activation, thus preventing autoimmunity.

Role in Immune Synapse Formation:

• CD84 is involved in the formation of the immune synapse, the point of contact between immune cells such as T cells and antigen-presenting cells (APCs). It facilitates adhesion and signal transduction necessary for effective immune responses.
• The homophilic interaction of CD84 across cell surfaces enhances the adhesion between immune cells, supporting processes like antigen presentation and cell communication.

Regulation of Cytokine Production:

• CD84 signaling influences the production of various cytokines, such as IFN-γ and IL-10, which are critical for immune regulation. The activation or inhibition of CD84 can lead to differential cytokine profiles that either stimulate or dampen immune responses.
• In macrophages, CD84 is thought to play a role in modulating inflammatory responses, influencing the balance between pro-inflammatory and anti-inflammatory cytokine secretion.

Role in Platelet Activation:

• CD84 is also expressed on platelets, where it participates in the regulation of platelet aggregation and activation, contributing to processes like thrombosis and hemostasis.

Involvement in Lymphocyte Adhesion and Migration:

• CD84 regulates the adhesion of B and T lymphocytes to other immune cells, facilitating immune surveillance and interactions in secondary lymphoid organs like the spleen and lymph nodes.
• CD84 also influences the migration of immune cells through its impact on cell adhesion, making it important for immune cell trafficking to sites of infection or inflammation.

Clinical Issues

Autoimmune Diseases:

• Dysregulation of CD84 signaling has been implicated in several autoimmune diseases, including lupus and rheumatoid arthritis. Aberrant CD84 expression or function may lead to inappropriate immune activation, contributing to the pathogenesis of these disorders.
• Inhibitory signals mediated through CD84 could potentially be harnessed for therapeutic interventions in autoimmune diseases by promoting immune tolerance and reducing pathological inflammation.

Cancer:

• CD84 expression is altered in some cancers, and it has been studied for its role in regulating immune responses within the tumor microenvironment. Given its involvement in immune regulation, CD84 could either promote or inhibit tumor immunity, depending on the context.
• Targeting CD84 or its signaling pathways might represent a therapeutic strategy for modulating immune responses in cancer, either by enhancing anti-tumor immunity or reducing immune suppression.

Inflammatory Diseases:

• Due to its role in regulating inflammatory cytokine production, CD84 may be implicated in chronic inflammatory conditions. Dysregulated CD84 function in macrophages and other immune cells could contribute to chronic inflammation, making it a potential target in diseases like inflammatory bowel disease (IBD) or psoriasis.

Thrombosis and Hemostasis:

• Given its expression on platelets, CD84 could be involved in disorders of thrombosis or bleeding. Alterations in CD84 function may impact platelet activation and aggregation, influencing the risk of thromboembolic events or bleeding disorders.

Summary

CD84 is an important member of the SLAM family of receptors and plays a crucial role in the regulation of immune responses, particularly in lymphocytes, macrophages, and platelets. Structurally, it consists of two Ig-like extracellular domains, a single transmembrane region, and an intracellular domain containing ITSM motifs, which are critical for signaling and interaction with proteins such as SAP. Through its interactions with other SLAM family members and the modulation of signaling pathways, CD84 regulates immune cell activation, cytokine production, immune synapse formation, and cell adhesion.

In clinical contexts, CD84 is involved in the regulation of autoimmune diseases, cancer immunity, inflammatory conditions, and platelet-related disorders. Understanding the molecular mechanisms of CD84 function has the potential to reveal new therapeutic strategies for modulating immune responses in these diseases. Its dual role as both an activator and inhibitor of immune responses provides opportunities for fine-tuning immune modulation in a variety of pathological conditions.