The CD86gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily.Alternative splicing results in two transcript variants encoding different isoforms. Additional transcript variants have been described, but their full-length sequences have not been determined.
The binding of CD86 (or the closely related protein CD80) expressed on the surface of an antigen-presenting cell with CD28 on the surface of a mature, naive T-cell, is required for T-cell activation. This protein interaction, along with the primary signal that is the MHC class II with an attached peptide binding to the T-cell receptor (TCR), activates mitogen-activated protein kinase and transcription factor nf-κB in the T-cell. These proteins up-regulate production of CD40L (used in B-cell activation), IL-21 and IL-21R (used for division/proliferation), and IL-2, among other cytokines.
CTLA-4 inhibits CD86 - CD28 binding when active on T-regulatory cells
T-regulatory cells produce CTLA-4, which can dampen an immune response and lead to increased anergy. CTLA-4 binds to CD86 with greater affinity than CD28, which impairs the co-stimulation necessary for proper T-cell activation. When bound to CTLA-4, CD86 can be removed from the surface of an APC and onto the T-reg cell in a process called trogocytosis. Blocking this process with anit-CTLA-4 antibodies is useful for a specific type of cancer immunotherapy called cancer therapy by inhibition of negative immune regulation. Japanese immunologist Tasuku Honjo and American immunologist James P. Allison won the Nobel Prize in Physiology or Medicine in 2018 for their work on this topic.
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