CD86 belongs to the immunoglobulin superfamily of proteins that drive innate and adaptive immune responses. It is an 80kD co-stimulatory molecule for the priming and activation of naive and memory T-cells, respectively. CD86 is expressed on activated B- and T- cells, monocytes/macrophages, dendritic cells, and astrocytes. Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) stimulates T-cell activation and triggering of key pro-inflammatory cytokine responses through NF-kB, while subsequent engagement of CTLA-4 (also known as CD152) with these same ligands results in response attenuation. CD86 has also been shown to be involved in immunoglobulin class-switching and triggering of NK cell-mediated cytotoxicity.
With their central function in immune modulation, CD28- and CTLA-4-associated signaling pathways are primary therapeutic targets for preventing autoimmune disease, graft versus host disease (GVHD), inflammation, sepsis, and tumor immunity promotion. CD86, along with CD80 which is present on APCs such as dendritic cells (DCs), are both co-stimulatory molecules in the immune synapse. CD86 is expressed earlier in the immune response than CD80. A detailed review on the roles of CD86 and its CTLA-4 counterpart in tolerance regulation was published by Romo-Tena1. This review provides some recent insights into the delicate balance between the opposing systems with regards to autoimmune disease. Gregory et al relied upon the CD86 antibody to profile down-regulated genes in response to Kaposi’s sarcoma-associated Herpesvirus (KSHV)2. Their studies found that several host immune response genes - such as CD86, CD80, TNF-alpha, and IL-1B - were all down-regulated in a widespread suppression of key immune response factors. Baitsch’s group at the University of Lausanne used the CD86 antibody to analyze the expression of a panel of inhibitory receptors and their ligands3. Their data suggests that naïve T-cells are governed through BTLA- and TIM3-mediated pathways, while effector cells trigger much large numbers of receptors.
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