IL-28A, IL-28B, and IL-29, also named interferon-lambda2 (IFN-lambda2), IFN-lambda3, and IFN-lambda1, respectively, are newly identified class II cytokine receptor ligands that are distantly related to members of the IL-10 family (11-13% aa sequence identity) and the type I IFN family (15-19% aa 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 up-regulation of MHC class I antigen expression. The three proteins signal through the same heterodimeric receptor complex that is composed of the IL-10 receptor beta (IL-10 Rbeta) and a novel IL-28 receptor alpha (IL-28 Ralpha, also known as IFN-lambdaR1). Ligand binding to the receptor complex induces Jak kinase activation and STAT1 and STAT2 tyrosine phosphorylation.