Alternative titles; symbolsCD28 ANTIGEN LIGAND 2; CD28LG2B-LYMPHOCYTE ACTIVATION ANTIGEN B7-2; LAB7-2B72 ANTIGENHGNC Approved Gene Symbol: CD86Cytogenetic locati...
Alternative titles; symbols
HGNC Approved Gene Symbol: CD86
Cytogenetic location: 3q13.33 Genomic coordinates (GRCh38): 3:122,055,361-122,121,135 (from NCBI)
▼ Cloning and Expression
Induction of an immune response requires that T cells receive 2 sets of signals from antigen-presenting cells. The first signal is delivered through the T-cell receptor complex, while the second is provided by the B-cell activation antigens B7-1, or CD80 (112203), and B7-2, or CD86, by interaction with the T-cell surface molecules, CD28 (186760) and CTLA4 (123890). A cDNA for B7-2 was obtained by Freeman et al. (1993). B7-2 mRNA is constitutively expressed in unstimulated B cells. The predicted protein is a type I membrane protein of the immunoglobin superfamily.
Jeannin et al. (2000) detected a soluble form of CD86 in human serum that could be generated either by shedding of the membrane form or through alternative splicing. RT-PCR analysis revealed the expression of 2 transcripts in nonstimulated monocytes but only the full-length transmembrane form in activated monocytes. The smallest transcript, 828 bp, which the authors termed CD86deltaTM, has a deletion from nucleotide 686 to nucleotide 829 (i.e., exon 6) and encodes a 275-amino acid protein. SDS-PAGE and Western blot analysis detected expression of CD86 and CD86deltaTM in COS cells as 65- and 48-kD proteins, respectively. FACS analysis detected only CD86 transfected cells and ELISA analysis detected only CD86deltaTM in cell-free supernatants. Binding analysis demonstrated that CD86deltaTM binds to CD28- or CTLA4-expressing cells. Functional analysis indicated that CD86deltaTM enhances proliferation and cytokine production by both naive and memory T cells.
▼ Gene Function
Resting eosinophils express neither MHC class II proteins or costimulatory B7 molecules and fail to induce proliferation of T cells to antigens. Celestin et al. (2001) reported that IL3 (147740) induces expression of HLA-DR and B7.2 on eosinophils, but, unlike IL5 (147580) and GMCSF (CSF2; 138960), it does not induce expression of B7.1. IL3-treated eosinophils supported modest T-cell proliferation in response to superantigen toxic shock syndrome-1 antigen, as well as proliferation of HLA-DR-restricted T-cell clones to tetanus toxoid (TT) and influenza virus antigenic peptides. The response was blocked by anti-B7.2 monoclonal antibody. IL3-treated eosinophils were unable to present native TT antigen to either resting or TT-specific cloned T cells. Parallel experiments established that IL5 and GMCSF induce T-cell proliferation to peptides but not to native TT antigen. Celestin et al. (2001) suggested that eosinophils activated by IL3 may contribute to T-cell activation in allergic and parasitic diseases by presenting superantigens and peptides to T cells.
An immune response against thyroid carcinoma could be important for long-term survival. Gupta et al. (2001) reported that infiltration of thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival. Shah et al. (2002) hypothesized that the antigen presentation coactivators B71 (112203) and B72, which are important in other immune-mediated thyroid diseases, might be important in lymphocytic infiltration of thyroid carcinoma. To test this, they determined B71 and B72 expression by immunohistochemistry in 27 papillary (PTC) and 8 follicular (FTC) thyroid carcinomas (see 188550) and 9 benign thyroid lesions. B72 expression was of similar intensity in benign and malignant tumors, but was more intense than in presumably normal adjacent thyroid. B72 expression also correlated with the number of tumor-associated lymphocytes per high-power field. Recurrence developed exclusively from tumors that expressed B72, and intense B72 expression was associated with a reduced probability of remission. Shah et al. (2002) concluded that these data support the hypothesis that the antigen presentation coactivators B71 and B72 may be important for lymphocytic infiltration and the immune response against thyroid carcinoma.
▼ Biochemical Features
Schwartz et al. (2001) reported the crystal structure of the complex between the disulfide-linked homodimer of human CTLA4 (123890) and the receptor-binding domain of human B7.2 at 3.2-angstrom resolution.
▼ Gene Structure
Jellis et al. (1995) isolated the gene for B7-2, which is composed of 8 exons and spans more than 22 kb. The authors found that alternatively spliced cDNAs result from the use of either exon 1 or 2. Exon 3 corresponds to the signal peptide, exon 4 to an IgV-like domain, exon 5 to an IgC-like domain and exon 6 corresponds to the transmembrane region and part of the cytoplasmic tail. Exons 7 and 8 encode the remainder of the tail.
Reeves et al. (1997) demonstrated that the CD86 and CD80 genes are linked on human chromosome 3 and mouse chromosome 16. Reeves et al. (1997) used fluorescence in situ hybridization mapping to show that CD86, like CD80, maps to human 3q21 and mouse chromosome 16, band B5.