Publisher Summary CD86 is expressed at high levels on resting peripheral blood monocytes and dendritic cells and at very low levels on resting B and T cells. Activation of B cells, T cells, and monocytes and culture of Langerhans cells lead to increased expression of CD86. The CD86 expression is induced more rapidly than the CD80 expression (peaks at ∼20 h versus ∼60 h) and reaches higher levels. The expression is increased by IL-4 (B cells) and IFNγ (peripheral blood monocytes) and decreased by IL-10 (peripheral blood dendritic cells). CD86 is an IgSF molecule structurally related to CD80 (25% amino acid identity). The extracellular domain contains two IgSF domains and is highly glycosylated. The transmembrane domain contains two of the three cysteines seen in CD80. The cytoplasmic domain is completely unrelated to the CD80 cytoplasmic domain and contains three potential protein kinase C phosphorylation sites. The interactions of CD80 and CD86 with CD28 provide important costimulatory signals for T cells activated through the CD3/TCR. CD86 is expressed earlier than CD80 and appears to dominate in the primary immune response. Mice deficient in CD86 have more profound defects in T cell function (including T cell-dependent antibody responses) than CD80-deficient mice.