CD81 Gene

The CD81 gene (CD81 stands for "cluster of differentiation 81) is a protein-coding gene located on chromosome 11p15.5. Two transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene belongs to the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell surface proteins characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in regulating cell development, activation, growth, and motility. The encoded protein is a cell surface glycoprotein known to complex with integrins.

The CD81 protein appears to promote muscle cell fusion and support myotube maintenance. It may also be involved in signal transduction. This gene is localized in the tumor suppressor gene region, making it a candidate gene for malignancies.

The CD 81 protein represents a structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs) that serve as a platform for receptor clustering and signal transduction. The CD81 protein is essential for trafficking and compartmentalization of the CD19 receptor on the surface of activated B cells (van Zelm MC et al. 2010).

Upon initial encounter with microbial antigens, it facilitates the assembly of CD19-CR2/CD21 and B cell receptor (BCR) complexes at signaling TERMs, thereby lowering the threshold dose of antigen required to trigger clonal expansion of B cells and antibody production (Cherukuri A et al. 2004).

CD81 acts as a receptor for hepatitis C virus (HCV) in hepatocytes. CD81 forms the CLDN1-CD81 receptor complex with CLDN1. This is essential for hepatitis C virus entry into the host cell. Furthermore, CD 81 is specifically required for the infectivity of hepatocytes by Plasmodium falciparum and controls the entry of sporozoites into hepatocytes via the parasitophorous vacuoles and the subsequent differentiation of the parasites into exoerythrocytic forms.

The CD81 protein is present in MHC class II compartments and may also play a role in antigen presentation. In T cells, it facilitates localization of CD247/CD3 zeta at antigen-induced synapses with B cells, providing cost stimulation and polarization toward the T helper type 2 phenotype (Rocha-Perugini Vet al. 2013).

In myoblasts, it associates with CD9 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, it associates with CD9 and beta-1 and beta-2 integrins and prevents fusion of macrophages to multinucleated giant cells specialized for uptake of large complement-opsonized particles. Also prevents fusion of mononuclear cell precursors to osteoclasts responsible for bone resorption (Takeda Y et al. 2003). CD81 is also involved in cell adhesion and motility. Positively regulates integrin-mediated adhesion of macrophages, which is particularly relevant to the inflammatory response in the lung.

Diseases associated with CD81 include immunodeficiency, common variable 6 (CVID6).

1. Cherukuri A et al (2004) B cell signaling is regulated by induced palmitoylation of CD81. J Biol Chem 279:31973-31982.
2. Rocha-Perugini Vet al (2013) CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses. Mol Cell Biol 33:3644-3658.
3. Takeda Y et al (2003) Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. J Cell Biol 161:945-956).
4. van Zelm MC et al (2010) CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest 120:1265-1274