CD58 - CD58 molecule |Elisa - Clia - Antibody - Protein

Background

CD58, also known as Lymphocyte Function-associated Antigen 3 (LFA-3), is a cell surface glycoprotein primarily involved in cell adhesion processes. It plays a critical role in the immune response by mediating the interaction between T cells and antigen-presenting cells (APCs). The CD58 protein is a member of the immunoglobulin (Ig) superfamily and is widely expressed on a variety of cell types, including epithelial cells, endothelial cells, lymphocytes, and dendritic cells. Its main binding partner is CD2, a receptor found on T cells and natural killer (NK) cells. This interaction is essential for the formation of the immune synapse, facilitating the activation of T cells and subsequent immune responses.

CD58’s role is especially important in antigen presentation, where it helps T cells to recognize and respond to foreign antigens. The molecule is involved in co-stimulation during T-cell receptor (TCR) engagement, enhancing the immune system's ability to respond to pathogens, tumors, and other immunological challenges.

Protein Structure

CD58 is a type I membrane protein that exists in both membrane-bound and soluble forms. Its structure is characterized by several distinct regions:

Extracellular Domain:

• The extracellular domain consists of two immunoglobulin-like domains: one V-set domain and one C2-set domain, which are typical features of the Ig superfamily. These domains are critical for mediating the interaction between CD58 and CD2. The V-set domain is primarily responsible for binding to CD2 and facilitates the adhesive interaction between T cells and APCs.

Transmembrane Domain:

• CD58 has a single transmembrane region that anchors the protein in the plasma membrane. This hydrophobic region spans the lipid bilayer, ensuring that the extracellular domain is appropriately presented on the cell surface for interaction with other immune cells.

Cytoplasmic Tail:

• The cytoplasmic tail of CD58 is relatively short and plays a role in intracellular signaling and localization. Although not directly involved in its adhesive function, the cytoplasmic region may interact with intracellular proteins to influence the stability and localization of CD58 on the cell membrane.

Glycosylation Sites:

• CD58 is heavily glycosylated, which enhances its stability and helps maintain its proper conformation. The glycosylation of CD58 is critical for its function and efficient cell-surface expression, which is necessary for optimal binding with CD2.

In addition to its membrane-bound form, CD58 can also be shed from the cell surface, generating a soluble form of the protein. This soluble form retains functional activity, allowing it to bind to CD2 in the absence of direct cell-cell contact, which may have implications for modulating immune responses in circulation.

Classification and Subtypes

CD58 belongs to the immunoglobulin (Ig) superfamily, a large group of proteins that share structural similarities with antibodies. Within this family, CD58 is classified as an adhesion molecule due to its primary role in mediating cell-cell interactions. Specifically, CD58 is a member of the Ig-like CAM (Cell Adhesion Molecule) subfamily, which includes proteins that facilitate cell adhesion in the immune system.

Although CD58 does not have multiple subtypes, it exists in two forms:

1. Membrane-bound form: Predominantly expressed on the cell surface, facilitating direct interactions between T cells and APCs.
2. Soluble form: Generated by proteolytic cleavage of the membrane-bound form. It retains the ability to interact with CD2 and may regulate immune responses in a non-cell-contact manner.

Function and Biological Significance

The primary function of CD58 is to mediate cell adhesion and enhance the interaction between T cells and APCs during the immune response. Its biological significance is particularly evident in the following roles:

T cell activation:

• CD58 plays a pivotal role in T cell activation by binding to its ligand, CD2, which is expressed on the surface of T cells and NK cells. The interaction between CD58 and CD2 strengthens the immune synapse formed between T cells and APCs, enhancing TCR signaling and the overall immune response.
• This interaction is particularly important for co-stimulation, a process required for full T cell activation. In the absence of co-stimulation, T cells may fail to respond or become anergic (unresponsive), which can compromise immune surveillance and defense against pathogens and tumors.

Immune Synapse Formation:

• The interaction between CD58 on APCs and CD2 on T cells contributes to the formation of the immune synapse, a specialized junction that forms between T cells and their target cells during antigen presentation. This synapse allows for the focused delivery of signals between the two cells, optimizing the activation and function of the immune response.
• CD58-CD2 interactions are important for T cell adhesion and the stabilization of the immune synapse, ensuring that the T cell remains in close contact with the APC long enough to receive activating signals.

Cytotoxicity:

• In addition to its role in T cell activation, CD58 also enhances the cytotoxic activity of NK cells by interacting with CD2. NK cells play a crucial role in innate immunity by recognizing and killing virus-infected cells and tumor cells. The CD58-CD2 interaction promotes NK cell adhesion to target cells, facilitating their destruction.

Immune Modulation:

• CD58 may also play a role in regulating the balance between immune activation and tolerance. By modulating the interaction between T cells and APCs, CD58 influences whether the immune response is amplified or downregulated. This makes it a key player in preventing inappropriate immune responses, such as autoimmunity, while still allowing robust defense against infections and malignancies.

Clinical Issues

Given its critical role in T cell activation and immune synapse formation, abnormalities in CD58 expression or function can have significant clinical consequences:

Cancer:

• CD58 expression has been implicated in several types of cancer. Some tumors, particularly hematologic malignancies such as lymphomas and leukemias, may downregulate CD58 expression as a mechanism to evade immune detection. By reducing CD58 levels, tumor cells can impair T cell activation and NK cell-mediated cytotoxicity, allowing them to escape immune surveillance.
• Conversely, therapies that enhance CD58-CD2 interactions, such as immunotherapies, aim to boost the immune system's ability to recognize and destroy tumor cells.

Autoimmune Diseases:

• Given its role in T cell activation, alterations in CD58 function may contribute to autoimmune diseases. Overexpression or dysregulated activity of CD58 could lead to excessive T cell activation, resulting in autoimmune attacks against the body’s own tissues. There is evidence that certain polymorphisms in the CD58 gene are associated with an increased risk of autoimmune conditions like multiple sclerosis (MS).

Infectious Diseases:

• CD58-CD2 interactions are important in controlling infections by promoting effective T cell and NK cell responses. In viral infections, pathogens may attempt to interfere with CD58 expression or function to evade immune detection. Conversely, enhancing CD58-CD2 interactions could be a therapeutic strategy to boost immune responses in infections where immune evasion occurs.

Summary

CD58 is a crucial cell adhesion molecule belonging to the immunoglobulin superfamily and plays a key role in mediating immune responses by interacting with CD2 on T cells and NK cells. This interaction enhances T cell activation, immune synapse formation, and cytotoxic responses, all of which are critical for efficient immune function. Structurally, CD58 consists of two immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail, with glycosylation aiding its stability and function.

Clinically, CD58 is implicated in several conditions, including cancer, where its expression may be downregulated to facilitate immune evasion, and autoimmune diseases, where dysregulation of its function may contribute to pathological immune responses. Understanding the structure and function of CD58 provides important insights into its role in immunity and its potential as a therapeutic target in immunological diseases.