CD226 molecule | Elisa - Clia - Antibody - Protein

Background

CD226, also known as DNAX Accessory Molecule-1 (DNAM-1), is a critical glycoprotein that plays a significant role in the immune system. It is encoded by the CD226 gene located on chromosome 18q22.3. This molecule is predominantly expressed on the surface of various immune cells, including natural killer (NK) cells, T cells, monocytes, and platelets. The expression of CD226 is crucial for the regulation and activation of immune responses against tumors and infections.

CD226 was initially identified due to its involvement in the adhesion and activation of NK cells and T cells. Its significance has expanded to various immunological processes, including cytotoxicity, cytokine production, and immune cell signaling. The interaction of CD226 with its ligands, such as CD155 (PVR) and CD112 (Nectin-2), is vital for the mediation of immune responses.

Protein Structure

CD226 is a type I transmembrane glycoprotein consisting of 336 amino acids. It has an extracellular region, a single transmembrane domain, and a short cytoplasmic tail. The extracellular region of CD226 comprises two immunoglobulin-like (Ig-like) domains: a V-set domain and a C2-set domain. These domains are critical for ligand binding and cell adhesion. The transmembrane domain anchors the molecule in the cell membrane, while the cytoplasmic tail contains signaling motifs essential for initiating intracellular signaling cascades upon ligand binding.

The structure of CD226 enables it to interact with its ligands, CD155 and CD112, facilitating the adhesion and activation of immune cells. This interaction is crucial for the immune synapse formation between NK cells or T cells and their target cells, promoting effective immune responses.

Classification and Subtypes

CD226 belongs to the immunoglobulin superfamily (IgSF), a large group of proteins involved in the recognition, binding, or adhesion processes of cells. Within this family, CD226 is classified under the V-set and C2-set domain-containing molecules. While CD226 itself does not have subtypes, its ligands, CD155 and CD112, have several isoforms generated through alternative splicing, which can influence their binding affinity and functional outcomes.

Function and Biological Significance

CD226 plays a pivotal role in the regulation of immune responses. Its primary functions include:

1. Immune Cell Adhesion and Activation: CD226 facilitates the adhesion of NK cells and T cells to their target cells through interactions with its ligands. This adhesion is crucial for the formation of the immune synapse, a specialized junction that enables efficient communication and signaling between immune cells and their targets.
2. Cytotoxicity: CD226 is involved in the activation of NK cells and cytotoxic T lymphocytes (CTLs), enhancing their ability to kill tumor cells and virally infected cells. The binding of CD226 to CD155 and CD112 triggers signaling pathways that lead to the release of cytotoxic granules and the induction of apoptosis in target cells.
3. Cytokine Production: CD226 signaling promotes the production of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which are essential for coordinating immune responses and enhancing the cytotoxic activity of NK cells and CTLs.
4. Immune Regulation: CD226 also plays a role in the regulation of immune responses by modulating the activity of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), which are critical for maintaining immune homeostasis and preventing excessive inflammation.

Clinical Issues

The expression and function of CD226 have been implicated in various clinical conditions, including:

1. Cancer: Alterations in CD226 expression or function can impact the immune surveillance and elimination of tumor cells. Loss or downregulation of CD226 expression on NK cells and T cells has been associated with poor prognosis in several cancers, including melanoma, leukemia, and colorectal cancer. Therapeutic strategies targeting the CD226 pathway are being explored to enhance anti-tumor immunity.
2. Autoimmune Diseases: Dysregulation of CD226 signaling has been linked to autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. Overactivation of CD226 can lead to excessive immune responses and tissue damage, highlighting its role in maintaining immune tolerance.
3. Infectious Diseases: CD226 is crucial for the immune response against viral infections. Impaired CD226 function can lead to reduced viral clearance and chronic infection. Understanding the role of CD226 in infectious diseases can aid in the development of novel therapeutic approaches to enhance antiviral immunity.

Summary

CD226 (DNAM-1) is a vital immunoregulatory molecule involved in the adhesion, activation, and cytotoxic function of NK cells and T cells. Its interaction with ligands CD155 and CD112 is essential for immune synapse formation and effective immune responses against tumors and infections. The dysregulation of CD226 expression or function is implicated in various clinical conditions, including cancer, autoimmune diseases, and infectious diseases. Ongoing research aims to elucidate the detailed mechanisms of CD226 signaling and develop targeted therapies to modulate its activity for therapeutic benefit. Understanding the multifaceted roles of CD226 in the immune system can pave the way for novel immunotherapeutic strategies in treating various diseases.