CD86 molecule | Elisa - Clia - Antibody - Protein

Background

CD86, also known as B7-2, is a transmembrane glycoprotein that plays a crucial role in the costimulatory signaling necessary for T-cell activation and immune response. It is a member of the immunoglobulin (Ig) superfamily and is encoded by the CD86 gene located on chromosome 3q21. CD86 is primarily expressed on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. The interaction of CD86 with its receptors, CD28 and CTLA-4 (CD152), on T cells is vital for regulating immune responses, influencing both the activation and inhibition of T cells.

Protein Structure

CD86 is a type I transmembrane protein composed of several key structural domains:

• Extracellular Domain: The extracellular region of CD86 comprises two immunoglobulin-like domains: one variable-like (IgV) domain and one constant-like (IgC) domain. These domains are responsible for binding to the CD28 and CTLA-4 receptors on T cells.
• Transmembrane Domain: This hydrophobic region spans the cell membrane, anchoring the protein to the cell surface.
• Intracellular Domain: The cytoplasmic tail of CD86 contains motifs essential for signal transduction. Though relatively short, it is critical for transmitting activation signals into the APC upon receptor engagement.

Classification and Subtypes

CD86 is part of the B7 family of costimulatory molecules, which also includes CD80 (B7-1), another critical ligand for CD28 and CTLA-4. There are no subtypes of CD86 itself, but its functional interactions with CD28 and CTLA-4 are significant for its role in immune modulation.

Function and Biological Significance

T-cell Activation:

• CD86 is crucial for the activation of T cells. When APCs present antigens to T cells via the major histocompatibility complex (MHC), the interaction of CD86 with CD28 on the T cells provides a necessary costimulatory signal. This interaction promotes T cell proliferation, cytokine production, and differentiation, enhancing the immune response.

Immune Regulation:

• The interaction of CD86 with CTLA-4, an inhibitory receptor on T cells, provides a counterbalance to the activation signal delivered by CD28. CTLA-4 binding to CD86 sends an inhibitory signal to the T cell, leading to reduced proliferation and cytokine production. This mechanism is essential for maintaining immune homeostasis and preventing overactivation that can lead to autoimmunity.

Immune Tolerance:

• CD86 plays a role in the induction of immune tolerance. The engagement of CTLA-4 by CD86 on regulatory T cells (Tregs) is vital for their suppressive function, helping to maintain tolerance to self-antigens and prevent autoimmune reactions.

B-cell Activation and Function:

• In addition to its role in T-cell activation, CD86 is involved in B-cell activation. The expression of CD86 on B cells enhances their ability to present antigens and receive help from T cells, which is crucial for antibody production and the humoral immune response.

Clinical Issues

Autoimmune Diseases:

• Dysregulation of CD86 expression or function can contribute to autoimmune diseases. Overexpression of CD86 can lead to excessive T cell activation and autoimmunity. Therapeutic strategies that target CD86 or its interactions with CD28/CTLA-4 are being explored to treat autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes.

Cancer:

• The role of CD86 in T cell activation makes it a target for cancer immunotherapy. Enhancing CD86 expression on dendritic cells can improve the activation of tumor-specific T cells, boosting anti-tumor immunity. Conversely, blocking the CD86-CTLA-4 interaction can enhance T cell responses against cancer cells. This approach is the basis for CTLA-4 blockade therapies, such as ipilimumab, used in cancer treatment.

Transplantation:

• In organ transplantation, modulating CD86 expression can influence graft acceptance or rejection. Strategies that block CD86 interactions can reduce T cell activation and prevent graft rejection, improving transplant outcomes.

Infectious Diseases:

• CD86 is involved in the immune response to infections. Its expression on APCs helps to activate T cells against pathogens. Therapeutic modulation of CD86 can enhance the immune response to infections or reduce immunopathology associated with excessive immune activation.

Summary

CD86 is a critical costimulatory molecule in the immune system, primarily involved in T-cell activation and immune regulation. Its structure includes an extracellular domain with Ig-like domains, a transmembrane region, and a short intracellular tail essential for signal transduction. CD86 interacts with CD28 and CTLA-4 on T cells to regulate their activation and inhibition, balancing immune responses. This balance is vital for effective immune function, preventing autoimmunity, and maintaining tolerance.

CD86 is implicated in various clinical conditions, including autoimmune diseases, cancer, transplantation, and infectious diseases. Therapeutic strategies targeting CD86 or its interactions are being developed to modulate immune responses in these conditions. Enhancing CD86-mediated activation or blocking its inhibitory pathways holds promise for improving treatments for autoimmune diseases, cancer immunotherapy, and transplant outcomes. The ongoing research into CD86 continues to uncover its diverse roles in immunology, offering new insights and potential therapeutic applications.