CD86

Official Full Name

CD86 molecule

Organism

Homo sapiens

GeneID

942

Background

This gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. This protein is expressed by antigen-presenting cells, and it is the ligand for two proteins at the cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte-associated protein 4. Binding of this protein with CD28 antigen is a costimulatory signal for activation of the T-cell. Binding of this protein with cytotoxic T-lymphocyte-associated protein 4 negatively regulates T-cell activation and diminishes the immune response. Alternative splicing results in several transcript variants encoding different isoforms.[provided by RefSeq, May 2011]

Synonyms

B70; B7-2; B7.2; LAB72; CD28LG2;

Bio Chemical Class

Immunoglobulin

Protein Sequence

MDPQCTMGLSNILFVMAFLLSGAAPLKIQAYFNETADLPCQFANSQNQSLSELVVFWQDQENLVLNEVYLGKEKFDSVHSKYMGRTSFDSDSWTLRLHNLQIKDKGLYQCIIHHKKPTGMIRIHQMNSELSVLANFSQPEIVPISNITENVYINLTCSSIHGYPEPKKMSVLLRTKNSTIEYDGVMQKSQDNVTELYDVSISLSVSFPDVTSNMTIFCILETDKTRLLSSPFSIELEDPQPPPDHIPWITAVLPTVIICVMVFCLILWKWKKKKRPRNSYKCGTNTMEREESEQTKKREKIHIPERSDEAQRVFKSSKTSSCDKSDTCF

Open

Disease

Diabetes mellitus, Rheumatoid arthritis, Transplant rejection

Approved Drug

1 +

Clinical Trial Drug

1 +

Discontinued Drug

1 +

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

The CD86 gene encodes a type I membrane protein that belongs to the immunoglobulin superfamily. Its extracellular domain contains both V-like and C2-like regions, which share approximately 25% amino acid homology. CD86 provides co-stimulatory signals for T cell activation by interacting with CD28 and CTLA-4 on the T cell surface. While binding to CTLA-4 reduces T cell activation, therefore controlling the degree of the immune response, binding of CD86 to CD28 enhances T cell activation, proliferation, and the secretion of cytokines including IL-2.

Not only does CD86 control T cells, but it also contributes to B cell function, immunological tolerance, early immune cell activation, and Using its interactions with CD28, CD86 stimulates the activation of naive T cells and controls whether T cells will launch an immunological response or stay inactive. Moreover, the interaction of CD86 with CTLA-4 controls T cell activation using transendocytosis, therefore restricting the co-stimulating signal from CD28 and so producing an immunosuppressive impact.

Role of CD86 in Immune Regulation

T cell activation in T cell immune responses depends on the interaction between CD86 and CD28. This signaling not only increases the expression of the IL-2 receptor, therefore improving the immune response, but also generates cytokines including IL-2. But CTLA-4 also controls T cell activation; it competes with CD28 for binding to CD86 and CD80, therefore reducing the co-stimulating impact of CD28 and stopping too strong immunological responses. Immune tolerance depends on the interaction between CD86 and CTLA-4, which also helps to avoid overactivation of T cells and autoimmune responses.

The low affinity of CD86 in transendocytosis helps it to dissolve readily from CTLA-4 during internalization, therefore allowing CTLA-4 to recycle and hence continue to reduce T cell activation. This technology guarantees a balanced immunological response using finely controlled control of the immune system.

CD86 and Tumor Immune Evasion

Immune evasion in tumors is intimately linked to CD86 expression. Many cancer types have CD86 expression greatly lowered on the surface of tumor cells; in certain situations, CD86 is mostly found in the cytoplasm or nucleus rather than the cell membrane. This reduces the capacity of tumor cells to efficiently activate certain T cells, therefore enabling their escape from immune control. Research on the expression of CD80 and CD86 on dendritic cells (DCs) and other antigen-presenting cells (APCs) has shown that the tumor microenvironment downregulates these expressions, therefore reducing T cell activation and encouraging tumor immune evasion.

Figure 1 illustrates the mechanisms of T cell activation and inhibition mediated by CD28 and CTLA-4. Figure 1. T cell activation and inhibition mediated by CD28 and CTLA-4 (He X, et al., 2020)

For instance, in non-small cell lung cancer, ovarian cancer, renal cell carcinoma, esophageal cancer, and cervical cancer, CD86 expression is significantly lower than in normal tissues and adjacent cancer tissues, with a predominant intracellular localization. Dendritic cells lost in tumors prevent an efficient anti-tumor immune response from being triggered. Important indicators of tumor immune evasion and possible therapeutic targets, the levels of CD80 and CD86 expression are intimately correlated with clinical pathological stages and patient prognosis.

Research on CD86 and CTLA-4 has attracted a lot of interest with the advent of immune checkpoint inhibitors. CTLA-4 inhibitors, such as Ipilimumab, have been approved for the treatment of advanced cancers such as melanoma. By blocking the interaction between CTLA-4 and CD86, the immunosuppressive effect is reversed, enhancing T cell-mediated anti-tumor activity. Moreover, antibody medications aimed against CD86 are under development, meant to control immunological reactions for the treatment of autoimmune disorders and cancer.

Treatment of severe COVID-19 sufferers is another use. Targeting CD80/CD86, Abatacept may reduce hyperactive immune responses by limiting the interaction between CD80/CD86 and T cells, therefore preventing acute lung damage and providing fresh ideas for the treatment of severe COVID-19. Abatacept can control the overactive T cell response by binding to CD86, therefore offering a possible new method for immunotherapy in COVID-19.

References:

Kennedy A, Waters E, Rowshanravan B, et al. Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation. Nat Immunol. 2022;23(9):1365-1378.
Du X, Liu M, Su J, et al. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res. 2018;28(4):433-447.
Halliday N, Williams C, Kennedy A, et al. CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4. Front Immunol. 2020;11:600000.
He X, Xu C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020 Aug;30(8):660-669.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry