Cluster of Differentiation 80, also called B7-1, is a member of cell surface immunoglobulin superfamily which plays key, yet distinct roles in the activation of T cells. It is the ligand for two different proteins on the T cell surface: CD28 and CTLA-4. Studies have shown that CTLA-4 binds mostly to CD80. The structure presents two extracellular domains: a membrane distal variable-like domain (IgV) and a membrane proximal Ig constant-like domain (IgC) along with an intracellular domain. Both IgV and IgC consist of anti-parallel beta sandwiches joined by a short linker region. CD80 is mostly expressed on the surface of antigen-presenting cells including activated B cells, macrophages and dendritic cells.
CD81, also known as TAPA-1 and Tetraspanin-28, belongs to the transmembrane 4 superfamily, also known as the tetraspanin family. Members of this family mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. CD81 is a widely expressed cell-surface protein involved in an astonishing variety of biologic responses. CD81 associates with a wide range of membrane proteins including CD151, TfR2, LDL R, PCSK9, Glypican 3, IFITM1, IGSF8/CD316, FPRP, and complexes of CD19-CD21. It is related to adhesion, morphology, activation, proliferation, and differentiation of B, T, and other cells. CD81 additionally functions as a receptor for the E2 glycoprotein of hepatitis C virus. The CD81-E2 interaction inhibits NK cell cytolytic activity, provides a co-stimulatory signal to T cells, and inhibits the maturation of plasmacytoid dendritic cells.
CD82, also known as KAI-1, structurally belongs to tetraspanin family while categorised as metastasis suppressor gene on functional grounds. KAI1/CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signalling. Downregulation of CD82 expression is associated with the advanced stages of many human cancers and correlates with the acquisition of metastatic potential. Recent studies suggest that complex mechanisms underlie CD82 loss of function, including altered transcriptional regulation, splice variant production and post-translational protein modifications, and indicate a central role for CD82 in controlling metastasis as a 'molecular facilitator'. The loss of KAI1/CD82 expression in invasive and metastatic cancers is due to a complex, epigenetic mechanism that probably involves transcription factors such as NFkappaB, p53, and beta-catenin. A loss of KAI1 expression is also associated with the advanced stages of many human malignancies and results in the acquisition of invasive and metastatic capabilities by tumour cells. Thus, KAI1/CD82 is regarded as a wide-spectrum tumor metastasis suppressor.
CD82 antigen, also known as Kai-1, is a widely expressed palmitoylated molecule of the tetraspanin superfamily. KAI1/CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signaling. CD82/Kai-1 is a component of the promiscuous TIMP-1 interacting protein complex on the cell surface of human adenocarcinoma cells and gives insight into tumorigenic metastatic potential. CD82/Kai-1 suppresses EMT in prostate cancer cells adhered to fibronectin leading to reduced cell migration and invasiveness. CD82/Kai-1 function is important for muscle stem cell function in muscular disorders. Overexpression of CD82/Kai-1 suppresses growth, migration and invasion of oral cancer cells and may be considered as a potential therapeutic target in oral cancer.
CD83 antigen is a single-pass type I membrane protein which contains one Ig-like V-type (immunoglobulin-like) domain. CD83 is expressed by activated lymphocytes; Langerhans cells and interdigitating reticulum cells. It contains one Ig-like V-type (immunoglobulin-like) domain. ; the soluble CD83 has the opposite effect and has an immune inhibitory capacity. Due to its immune inhibitory function; CD83 may play a significant role in antigen presentation or the cellular interactions that follow lymphocyte activation.
CD86; also known as B-lymphocyte activation antigen B7-2 (referred to as B70); is a member of the cell surface immunoglobulin superfamily. B7-2 exists predominantly as a monomer on cell surfaces and interacts with two co-stimulatory receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expressed on T cells; and thus induces the signal pathways which regulate T cell activation and tolerance; cytokine production; and the generation of CTL. It is indicated that contacts between B and T helper cells mediated by CD86 encourage signals for the proliferation and IgG secretion of normal B cells and B cell lymphomas. Recent study has revealed that CD86 also promotes the generation of a mature APC repertoire and promotes APC function and survival. CD86 has an important role in chronic hemodialysis; allergic pulmonary inflammation; arthritis; and antiviral responses; and thus is regarded as a promising candidate for immune therapy.
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