CD5 - CD5 molecule |Elisa - Clia - Antibody - Protein

Background

The CD5 molecule is a type I transmembrane glycoprotein primarily expressed on the surface of T cells and a subset of B cells known as B1a cells. CD5 functions as an immunomodulatory receptor, playing a critical role in T-cell activation, immune tolerance, and B-cell signaling. Its primary role is in regulating immune responses by controlling the threshold of antigen receptor signaling in both T and B cells. CD5 is also involved in maintaining the delicate balance between immune activation and immune tolerance, which prevents autoimmune responses while ensuring effective immunity.

CD5 belongs to the scavenger receptor cysteine-rich (SRCR) superfamily of receptors, a group of molecules known to be involved in diverse biological functions, including immunity, apoptosis, and cellular adhesion. CD5 is especially notable for its role as a negative regulator of T-cell receptor (TCR) and B-cell receptor (BCR) signaling. This regulatory capacity makes CD5 crucial in maintaining immune homeostasis.

CD5 is constitutively expressed on all T cells, both CD4+ (helper T cells) and CD8+ (cytotoxic T cells), as well as on the B1a subset of B cells. Interestingly, CD5 expression levels can be altered in response to certain diseases, including lymphoproliferative disorders, autoimmune diseases, and various types of infections, suggesting its involvement in disease pathogenesis and immune regulation.

Protein Structure

The CD5 protein is composed of 495 amino acids and has a molecular weight of approximately 67 kDa. It is a type I transmembrane glycoprotein, which means it contains a single membrane-spanning domain, with its N-terminal portion located extracellularly and the C-terminal domain located intracellularly.

Primary Structure

The CD5 protein can be divided into the following domains:

• Extracellular Domain: This is the largest domain of the CD5 molecule and consists of three scavenger receptor cysteine-rich (SRCR) domains, which are characteristic of the SRCR superfamily. These SRCR domains are involved in mediating protein-protein interactions, and they are believed to play a role in ligand binding. The specific ligands for CD5 have been proposed to include components of the BCR, TCR, and potentially pathogen-associated molecular patterns (PAMPs).
• Transmembrane Domain: CD5 contains a single hydrophobic transmembrane domain that anchors the molecule to the plasma membrane of immune cells.
• Cytoplasmic Domain: The intracellular portion of CD5 is shorter than the extracellular portion but plays a crucial role in signal transduction. This domain lacks intrinsic kinase activity but can interact with signaling molecules such as phosphatases and other kinases that modulate immune responses. The cytoplasmic tail contains multiple tyrosine residues, which are subject to phosphorylation during immune signaling. Upon phosphorylation, the intracellular domain of CD5 recruits inhibitory molecules, such as Src homology region 2 domain-containing phosphatase-1 (SHP-1), to negatively regulate TCR or BCR signaling.

Tertiary and Quaternary Structure

CD5 exists as a monomer on the cell surface and does not form homodimers or heterodimers with other proteins. However, it associates closely with the TCR-CD3 complex in T cells and the BCR complex in B1a cells. Its proximity to these complexes allows it to modulate immune receptor signaling in response to antigen binding.

Classification and Subtypes

CD5 is a member of the SRCR superfamily, a class of proteins characterized by the presence of one or more SRCR domains. This superfamily contains receptors involved in immune functions, apoptosis, and cellular adhesion. The SRCR domains of CD5 are highly conserved across species, indicating an evolutionarily conserved role in immune regulation.

There are no known subtypes of the CD5 molecule, but it is closely related to other SRCR family members, such as CD6, which also plays a regulatory role in T-cell activation. CD6, in particular, shares structural homology with CD5 and is involved in similar signaling pathways in T cells.

Function and Biological Significance

CD5 primarily functions as a negative regulator of antigen receptor signaling in both T cells and B1a cells, and it plays a key role in immune tolerance, thymic selection, and autoimmunity prevention.

T-cell Function

In T cells, CD5 is co-expressed with the TCR-CD3 complex and serves as a modulator of TCR signaling. When a TCR engages with its cognate antigen presented on an MHC molecule, the intracellular tail of CD5 becomes phosphorylated. This phosphorylation recruits negative regulators such as SHP-1, which in turn reduces the strength of the TCR signal. This is crucial in preventing overactivation of T cells, which could lead to autoimmune responses. CD5 also plays an essential role during thymic selection. During positive selection in the thymus, CD5 helps control the intensity of TCR signaling to ensure the survival of thymocytes that recognize self-MHC molecules with moderate affinity. Additionally, in negative selection, CD5 prevents the survival of thymocytes with overly strong responses to self-antigens, reducing the likelihood of autoimmunity.

B-cell Function

In B1a cells, which are involved in producing natural antibodies that provide early protection against infections, CD5 functions as a regulator of BCR signaling. CD5 dampens the signaling strength of the BCR, preventing excessive activation and the generation of autoantibodies, which could lead to autoimmune diseases.

Immune Regulation and Autoimmunity

CD5 is crucial in maintaining self-tolerance, preventing inappropriate immune responses against the body’s own tissues. Its regulatory role ensures that both T cells and B cells do not become overly activated in response to self-antigens, thereby preventing autoimmunity.

Moreover, CD5 interacts with CD72, a negative regulator of BCR signaling on B cells, suggesting a broader role in immunoregulation across both T and B cells.

Clinical Issues

CD5 has been implicated in various autoimmune diseases, cancers, and infections due to its role in regulating immune responses.

Autoimmune Diseases

Dysregulation of CD5 expression or function has been associated with autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). In these diseases, defects in CD5’s ability to downregulate TCR or BCR signaling may lead to excessive immune activation against self-antigens, contributing to chronic inflammation and tissue damage.

Cancer

CD5 expression is a hallmark of certain types of T-cell leukemias and lymphomas, such as chronic lymphocytic leukemia (CLL) and peripheral T-cell lymphoma. In CLL, CD5 is aberrantly expressed on B cells, which may contribute to the dysregulated survival and proliferation of malignant B cells. CD5 is also used as a diagnostic marker in these cancers, as its expression pattern can help differentiate between different lymphoid malignancies.

Infections

CD5 has been shown to modulate the immune response during infections. For example, in viral infections such as HIV or hepatitis C, CD5 expression may be altered, affecting the host's ability to control the infection. Furthermore, CD5 may play a role in regulating the immune response to chronic infections, preventing excessive immune-mediated tissue damage.

Summary

The CD5 molecule is a critical immunoregulatory receptor involved in maintaining immune tolerance and modulating antigen receptor signaling in both T cells and B1a cells. Structurally, CD5 is a type I transmembrane glycoprotein with three SRCR domains that interact with signaling molecules to dampen TCR and BCR signaling, ensuring immune homeostasis. CD5 plays an essential role in thymic selection and the prevention of autoimmunity. Dysregulation of CD5 function is associated with autoimmune diseases, cancers, and infections, making it a key molecule in immune system regulation. Understanding the structure and function of CD5 offers valuable insights into potential therapeutic approaches for treating immune-related disorders and lymphoid malignancies.