CD86 (B7-2): A Key Costimulatory Molecule in Immune Regulation and Disease
Explore the CD86 gene, its protein product, expression patterns, associated diseases, and clinical significance.
Gene Information Card
| Symbol | CD86 |
|---|---|
| Full Name | CD86 molecule |
| Gene Type | protein coding |
| Chromosomal Location | 3q13.33 |
| NCBI Gene ID | 942 ncbi.nlm.nih.gov/gene/942 |
| Ensembl ID | ENSG00000114013 |
| UniProt ID | P42081 |
| OMIM ID | 601025 |
| HGNC ID | 1705 |
| Aliases | B7-2, B70, CD28LG2, LAB7-2, B7.2 |
Description
CD86 (Cluster of Differentiation 86), also known as B7-2, is a type I membrane protein that serves as a costimulatory ligand for CD28 and CTLA-4 receptors on T cells. It is expressed on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells, and plays a critical role in regulating T cell activation and tolerance. CD86 provides the second signal required for optimal T cell proliferation and cytokine production, while its interaction with CTLA-4 delivers inhibitory signals. Aberrant CD86 expression is implicated in autoimmune diseases, transplant rejection, and tumor immune evasion, making it a target for therapeutic interventions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus) | Altered CD86 expression on APCs leads to enhanced T cell activation and breakdown of self-tolerance. | Multiple studies show increased CD86 on B cells and dendritic cells in autoimmune patients; GWAS links CD86 variants to SLE. |
| Cancer (various types) | Tumor cells or tumor-infiltrating APCs may upregulate CD86 to engage CTLA-4, promoting immune suppression; alternatively, loss of CD86 reduces costimulation, aiding immune evasion. | Immunohistochemistry and flow cytometry show variable CD86 expression in tumors; checkpoint blockade targeting CTLA-4 (which binds CD86) is clinically effective. |
| Transplant rejection | CD86 on donor APCs stimulates recipient T cells, contributing to allograft rejection. | Animal models show that CD86 blockade prolongs graft survival; clinical trials with anti-CD86 antibodies are ongoing. |
| Infectious diseases (e.g., HIV, tuberculosis) | Pathogens modulate CD86 expression to evade or exploit immune responses. | Studies show altered CD86 levels on monocytes in HIV and TB patients, affecting T cell responses. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High (e.g., 50-100 nTPM) | High expression in germinal centers and APCs. |
| Spleen | High (e.g., 40-80 nTPM) | High expression in marginal zone and white pulp. |
| Bone marrow | Moderate (e.g., 20-40 nTPM) | Expressed on developing B cells and myeloid precursors. |
| Blood | Moderate (e.g., 15-30 nTPM) | Expressed on monocytes, B cells, and dendritic cells. |
| Lung | Low (e.g., 5-15 nTPM) | Alveolar macrophages express CD86. |
| Liver | Low (e.g., 2-10 nTPM) | Kupffer cells express CD86. |
| Brain | Very low (e.g., <2 nTPM) | Microglia may express CD86 upon activation. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | ~20 nTPM | Constitutive expression; upregulated by LPS. |
| Raji (Burkitt lymphoma B cells) | ~30 nTPM | High expression; used as APC model. |
| MCF7 (breast cancer) | ~5 nTPM | Low expression; may be induced by cytokines. |
| HeLa (cervical cancer) | ~3 nTPM | Low basal expression. |
| Jurkat (T cell leukemia) | ~1 nTPM | Minimal expression; not typical for T cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1129055 (c.943A>G, p.Ile315Val) | SNP (missense) | Minor allele frequency ~0.2-0.4 in various populations | May affect CD86 function; associated with autoimmune disease susceptibility in some studies. |
| rs2715267 (intronic variant) | SNP (intronic) | Common (MAF >0.1) | Linked to altered CD86 expression in immune cells; potential disease association. |
| rs1913514 (5' UTR variant) | SNP (regulatory) | Common (MAF ~0.3) | May influence transcription factor binding and CD86 levels. |
| Somatic mutations in cancer (e.g., in COSMIC) | Missense, nonsense, frameshift | Rare (<1% in most cancer types) | May disrupt CD86 function, contributing to immune evasion; functional impact often unknown. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD86 are rare and not well characterized. Complete deficiency would impair T cell costimulation, potentially leading to immunodeficiency, but no such germline mutations have been reported in humans. Somatic loss in tumors may reduce anti-tumor immunity.
Gain of Function (GOF)
Gain-of-function mutations that increase CD86 expression or affinity for CD28 could enhance T cell activation, potentially exacerbating autoimmunity. However, no specific gain-of-function variants have been confirmed.
Dominant Negative (DN)
Dominant-negative effects are unlikely for CD86, as it functions as a membrane-bound ligand; however, soluble splice variants may act as decoys, but these are not well documented.
View complete mutation data：
Gene Ontology (GO)
| • immune response | • T cell costimulation |
| • signal transduction | • cell surface receptor signaling pathway |
| • protein binding | • identical protein binding |
| • receptor ligand activity | • plasma membrane |
| • integral component of membrane |
Pathways
• T cell receptor signaling pathway
• Costimulation by the CD28 family
• PD-1 signaling
• CTLA-4 inhibitory signaling
• Antigen processing and presentation
Protein Summary
CD86 is a type I transmembrane glycoprotein of 329 amino acids (UniProt P42081). It consists of an extracellular region with two immunoglobulin-like domains (V and C2), a transmembrane domain, and a short cytoplasmic tail. The protein is expressed on the surface of antigen-presenting cells and binds to CD28 and CTLA-4 on T cells. CD86 is constitutively expressed at low levels but is rapidly upregulated upon activation. Its interaction with CD28 provides a costimulatory signal essential for T cell activation, while binding to CTLA-4 delivers inhibitory signals, thus fine-tuning immune responses. CD86 also exists in soluble forms generated by alternative splicing or proteolytic cleavage, which may modulate immune function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD86 Knockout HEK293 Cell Line | EDJ-KQ17701 | Human | 942 | Details Get a Quote |
| CD86 Knockout HeLa Cell Line | EDJ-KQ52830 | Human | 942 | Details Get a Quote |
| CD86 Knockout A-549 Cell Line | EDJ-KQ61300 | Human | 942 | Details Get a Quote |
| CD86 Knockout HCT 116 Cell Line | EDJ-KQ69795 | Human | 942 | Details Get a Quote |
| CD86 Overexpression K-562 Stable Cell Line | EDC90669 | Human | 942 | Details Get a Quote |
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