IL-28A, IL-28B, and IL-29, also named interferon-lambda 2 (IFN-lambda 2), IFN-lambda 3, and IFN-lambda 1, respectively, are newly identified class II cytokine receptor ligands that are distantly related to members of the IL-10 family (11-13% a.a. sequence identity) and the type IIFN family (15-19 % a.a. sequence identity). The expression of IL-28A, B, and IL-29 is induced by virus infection or double-stranded RNA. All three cytokines exert bioactivities that overlap those of type I IFNs, including antiviral activity and upregulation of MHC class I antigen expression. The three proteins signal through the same heterodimeric receptor complex that is composed of the IL-10 receptor lambda (IL-10 R beta) and a novel IL-28 receptor alpha (IL-28 R alpha, also known as IFN-lambda R1). Ligand binding to the receptor complex induces Jak kinase activation and STAT1 and STAT2 tyrosine phosphorylation.