Recombinant Human IL-28A/IFN-lambda 2 Protein

IL-28A, IL-28B, and IL-29, also named interferon-lambda 2 (IFN-lambda 2), IFN-lambda 3, and IFN-lambda 1, respectively, are class II cytokine receptor ligands that are distantly related to members of the IL-10 family (11-13% aa sequence identity) and type I IFN family (15-19% aa sequence identity) (1-3). The genes encoding these three cytokines are localized to chromosome 19 and each is composed of multiple exons. The exon organization of these genes is also found in the IL-10 family genes but is distinct from the type I IFNs, which are encoded within a single exon. 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 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. The phosphorylated STAT1 and STAT2 complex with IFN-regulatory factor 9 (IRF-9) to form the IFN-stimulated regulatory factor 3 (ISGF-3) transcription factor complex that is translocated to the nucleus. ISGF-3 binds to the IFN-stimulated response element (ISRE) present in the regulatory regions of the target genes. Human IL-28A cDNA encodes a 200 amino acid (aa) residue precursor protein with a putative 25 aa signal peptide. It shares 94% and 67% aa sequence identity with human IL-28B and human IL-29, respectively.