CD81 - CD81 molecule |Elisa - Clia - Antibody - Protein

Background

CD81, also known as TAPA-1 (Target of the Anti-Proliferative Antibody 1), is a member of the tetraspanin family, a group of proteins that are widely expressed across various tissues and cell types. Tetraspanins are integral membrane proteins involved in a variety of biological processes, including cell adhesion, migration, proliferation, and signal transduction. CD81 has a well-established role in immune cell function, particularly in the regulation of B and T cell activity, as well as in viral infections. Most notably, CD81 is a critical component in the entry process of hepatitis C virus (HCV) into host cells.

The CD81 gene is located on chromosome 11p15.5 and encodes a protein that is involved in the formation of tetraspanin-enriched microdomains. These microdomains facilitate the assembly of various signaling complexes at the cell membrane, influencing the function of associated proteins. CD81 is widely expressed on multiple cell types, including lymphocytes, hepatocytes, epithelial cells, and fibroblasts.

Protein Structure

CD81 is a tetraspanin protein, which means it spans the plasma membrane four times, creating a structure that contains four transmembrane domains. The molecular weight of CD81 is approximately 25 kDa, and it is characterized by its short cytoplasmic N- and C-terminal domains, four transmembrane helices, and two extracellular loops (EC1 and EC2).

1. Transmembrane Domains:

• CD81 has four transmembrane helices that anchor the protein in the plasma membrane, contributing to its stability and positioning. These domains are important for the protein’s ability to interact with the lipid bilayer of the membrane.
• These transmembrane regions also participate in protein-protein interactions, facilitating the formation of tetraspanin-enriched microdomains. Such interactions allow CD81 to associate with other tetraspanins and various integrins, as well as signaling molecules.

1. Extracellular Domains:

• CD81 has two extracellular loops: a small loop (EC1) and a large loop (EC2). The EC2 loop is particularly important for its biological function, as it contains several critical sites for protein-protein interactions and is essential for CD81’s role in viral entry, including HCV entry into hepatocytes.
• The EC2 loop contains highly conserved cysteine residues that form disulfide bonds, stabilizing the loop’s structure and providing the protein with its functional capacity.
• The large extracellular loop is involved in binding to other membrane proteins, such as CD19 (involved in B cell function), and plays a role in the clustering of surface molecules during immune cell activation.

1. Cytoplasmic Domains:

• CD81 contains short cytoplasmic N- and C-terminal tails, which participate in intracellular signaling and trafficking. These domains can also be involved in interactions with cytoskeletal proteins, which assist in the localization and function of CD81 at the cell surface.

Classification and Subtypes

CD81 belongs to the tetraspanin family of proteins, which includes more than 30 members. Tetraspanins are classified based on their four transmembrane domains and their ability to form tetraspanin-enriched microdomains. These microdomains act as scaffolding platforms for a wide variety of cell surface receptors, integrins, and other signaling molecules.

CD81 does not have subtypes in the classical sense, but it does form distinct functional complexes by interacting with different proteins in various cellular contexts. For example, in B cells, CD81 forms part of the B cell co-receptor complex along with CD19, CD21, and CD225, playing a critical role in B cell activation and proliferation.

Function and Biological Significance

CD81 is a multifunctional protein that plays important roles in several key biological processes, including immune cell regulation, cell adhesion, migration, and viral infection.

Immune Cell Function:

• CD81 is crucial for the regulation of B cell activation and proliferation. It forms part of the B cell co-receptor complex and enhances the signaling capability of CD19. This interaction lowers the threshold for B cell receptor (BCR) activation, allowing for a more sensitive immune response.
• In T cells, CD81 plays a role in cell adhesion and motility, promoting T cell activation and immune synapse formation. It is also involved in T cell costimulation, facilitating interactions with antigen-presenting cells (APCs).

Tetraspanin-Enriched Microdomains:

• CD81 is a key player in the formation of tetraspanin-enriched microdomains (TEMs) on the plasma membrane. These specialized regions are essential for the clustering and organization of various cell surface receptors and signaling proteins, which can regulate processes like cell adhesion and migration.
• By organizing integrins and other signaling molecules into these microdomains, CD81 helps control cell motility, making it important in processes such as immune surveillance and tissue repair.

Hepatitis C Virus (HCV) Entry:

• CD81 is best known for its role in viral infections, particularly in the entry of hepatitis C virus (HCV) into hepatocytes. CD81 acts as a receptor for the HCV envelope glycoprotein E2, allowing the virus to attach to host cells and initiate infection. Blocking the interaction between CD81 and the HCV E2 glycoprotein is a major target for therapeutic strategies aimed at preventing or treating HCV infection.

Cell Migration and Adhesion:

• CD81 regulates cell adhesion and migration through its interaction with integrins, a family of proteins involved in cell attachment to the extracellular matrix (ECM). By clustering integrins at the cell surface, CD81 enhances cell motility, contributing to processes such as wound healing and tissue regeneration.
• In the context of immune responses, CD81 facilitates the movement of immune cells to sites of inflammation or infection by promoting cell motility.

Clinical Issues

CD81 has been implicated in various disease processes, ranging from viral infections to cancer and immune disorders. The molecule’s broad range of functions in immune regulation and cell signaling make it a key player in several pathological conditions.

Hepatitis C Virus (HCV) Infection:

• CD81 is a critical receptor for HCV entry into host cells, particularly hepatocytes. The interaction between the HCV envelope glycoprotein E2 and CD81 is essential for the virus to establish infection. As a result, CD81 has become a therapeutic target for anti-HCV treatments.
• Several experimental therapies aim to block the CD81-E2 interaction, thereby preventing the virus from entering cells and reducing viral replication.

Cancer:

• CD81 is implicated in tumorigenesis due to its role in cell proliferation and migration. Dysregulation of CD81 expression has been observed in various cancers, including breast, lung, and colorectal cancers.
• In some cancers, CD81 expression is associated with tumor progression and metastasis, making it a potential biomarker for cancer diagnosis or prognosis.
• In B cell malignancies, such as non-Hodgkin lymphoma, CD81 expression plays a role in the dysregulation of B cell signaling pathways.

Immune Disorders:

• Given its role in immune cell regulation, CD81 is involved in autoimmune diseases and immune deficiencies. Dysregulation of CD81 expression or function can lead to aberrant immune responses.
• In systemic lupus erythematosus (SLE), altered CD81 expression on B cells has been linked to B cell hyperactivity and autoantibody production.

Therapeutic Targeting:

• CD81 is a promising therapeutic target in several diseases, particularly HCV infection and certain cancers. Monoclonal antibodies targeting CD81 or small molecules that disrupt CD81 interactions with other proteins are being explored as potential therapies.

Summary

CD81 is a member of the tetraspanin family, widely expressed across different cell types and playing a significant role in immune cell regulation, viral entry, and cell migration. Structurally, CD81 has four transmembrane domains, two extracellular loops, and short cytoplasmic tails, which allow it to participate in forming tetraspanin-enriched microdomains and interacting with other cell surface receptors like integrins and CD19.

Functionally, CD81 is essential for B and T cell regulation, cell adhesion, and migration, and it plays a pivotal role in the entry of hepatitis C virus (HCV) into host cells. It is also involved in processes such as immune synapse formation and antigen presentation.

Clinically, CD81 is a key player in HCV infection, making it an attractive target for antiviral therapies. Its role in cancer and immune disorders further underscores its importance as a therapeutic target in various pathological conditions.