CD80 molecule | Elisa - Clia - Antibody - Protein

Background

CD80, also known as B7-1, is a protein encoded by the CD80 gene in humans. It is an essential costimulatory molecule expressed on the surface of antigen-presenting cells (APCs) such as dendritic cells, B cells, and macrophages. CD80 plays a critical role in the regulation of immune responses by providing the necessary second signal for T cell activation and survival. This molecule interacts with CD28 and CTLA-4 receptors on T cells, mediating various immune responses. The discovery and understanding of CD80 have significant implications for immunology, particularly in the context of autoimmune diseases, transplant rejection, and cancer immunotherapy.

Protein Structure

CD80 is a type I transmembrane glycoprotein composed of 288 amino acids. Its structure is characterized by several key regions:

• Extracellular Domain: The extracellular region of CD80 consists of two immunoglobulin-like domains: a V-set domain and a C1-set domain. These domains are crucial for binding to the CD28 and CTLA-4 receptors on T cells. The V-set domain is involved in ligand binding, while the C1-set domain supports the structural integrity of the protein. Glycosylation sites within the extracellular domain contribute to the protein's stability and function.
• Transmembrane Domain: The transmembrane region anchors CD80 in the cell membrane. This hydrophobic segment spans the lipid bilayer, ensuring the proper orientation of the extracellular and intracellular domains.
• Intracellular Domain: The intracellular tail of CD80 is relatively short and lacks significant signaling motifs. However, it plays a role in the intracellular trafficking and surface expression of the protein.

Classification and Subtypes

CD80 belongs to the immunoglobulin superfamily due to its characteristic immunoglobulin-like domains. It is one of the key members of the B7 family of costimulatory molecules, which also includes CD86 (B7-2). Unlike CD80, which is constitutively expressed at low levels and can be upregulated upon activation, CD86 is expressed more broadly and rapidly upregulated upon immune activation.

Function and Biological Significance

T Cell Activation:

• CD80 provides a critical second signal necessary for T cell activation. Upon antigen recognition by the T cell receptor (TCR), the engagement of CD80 with CD28 on T cells enhances T cell proliferation, cytokine production, and survival. This costimulatory signal is vital for initiating robust immune responses.

Immune Checkpoint Regulation:

• CD80 interacts with CTLA-4 (cytotoxic T lymphocyte-associated protein 4), an inhibitory receptor on T cells. Binding of CD80 to CTLA-4 transmits an inhibitory signal, dampening T cell activation and maintaining immune homeostasis. This interaction is crucial for preventing autoimmune reactions and controlling the intensity of immune responses.

Regulation of Immune Responses:

• The balance between CD80-CD28 and CD80-CTLA-4 interactions regulates the immune response. CD80-CD28 interaction promotes immune activation, while CD80-CTLA-4 interaction inhibits T cell responses. This dynamic balance is essential for ensuring that immune responses are appropriately regulated to prevent overactivation or insufficient activation.

Role in Autoimmunity and Transplantation:

• Dysregulation of CD80 expression or function can contribute to autoimmune diseases, where an overactive immune response targets self-antigens. In transplantation, CD80-mediated costimulation plays a role in graft rejection. Blocking CD80-CD28 interactions can help induce tolerance and improve graft survival.

Cancer Immunotherapy:

• CD80 has emerged as a target in cancer immunotherapy. Strategies to enhance CD80 expression or function can boost anti-tumor immunity by promoting T cell activation. Conversely, blockade of CD80-CTLA-4 interactions using immune checkpoint inhibitors (e.g., ipilimumab) can unleash T cell responses against tumors.

Clinical Issues

Autoimmune Diseases:

• Overexpression or aberrant signaling through CD80 can contribute to autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Therapeutic strategies targeting CD80-CD28 interactions, such as abatacept (a CTLA-4-Ig fusion protein), have shown efficacy in treating these conditions by modulating T cell activation.

Transplant Rejection:

• In organ transplantation, CD80 plays a pivotal role in graft rejection by facilitating T cell-mediated immune responses against the transplanted tissue. Targeting CD80 or its interactions with CD28 has been explored to promote immune tolerance and prevent rejection.

Cancer:

• CD80 expression on tumor cells or APCs can influence anti-tumor immunity. Cancer immunotherapies, including immune checkpoint inhibitors targeting CTLA-4, leverage the regulatory role of CD80 to enhance T cell responses against tumors. Understanding the expression and function of CD80 in the tumor microenvironment is critical for developing effective immunotherapies.

Infectious Diseases:

• CD80-mediated costimulation is crucial for mounting effective immune responses against pathogens. Modulating CD80 interactions can influence the outcome of infectious diseases, potentially offering therapeutic avenues for enhancing pathogen clearance or controlling excessive inflammation.

Summary

CD80 (B7-1) is a fundamental costimulatory molecule essential for T cell activation and immune regulation. Its interactions with CD28 and CTLA-4 on T cells determine the balance between immune activation and inhibition, playing a crucial role in maintaining immune homeostasis. The structural features of CD80, including its immunoglobulin-like domains, transmembrane region, and intracellular tail, enable its function in immune signaling. CD80's involvement in autoimmune diseases, transplantation, cancer immunotherapy, and infectious diseases underscores its clinical significance. Therapeutic strategies targeting CD80 interactions offer promising avenues for modulating immune responses in various pathological conditions. Understanding the molecular mechanisms and regulatory roles of CD80 continues to be a critical area of research in immunology and clinical medicine.