Recombinant Human IL-28 R alpha/IFN-lambda R1 Fc Chimera, CF

IL-28 R alpha (IL-28 receptor alpha subunit; also named interferon-lambda R1) is a type I transmembrane glycoprotein that is the cytokine receptor family 2 member 12 (CRF2-12) (1 - 4). It pairs with the IL-10 receptor beta subunit (IL-10 R beta, CRF2-4) to form the IL-28 R (1 - 4). Each subunit of this receptor can interact with the interferon-like cytokines (type III interferons) IL-28A (IFN-lambda 2), IL-28B (IFN-lambda 3) or IL-29 (IFN-lambda 1) (1 - 4). Human IL-28 R alpha cDNA encodes a 520 amino acid (aa) protein with a 20 aa signal peptide, a 208 aa extracellular domain (ECD) with a fibronectin type III motif and four potential N-glycosylation sites, a 21 aa transmembrane sequence, and a proline-rich and acidic 271 aa cytoplasmic domain. Eight isoforms have been sequenced, but their significance is unknown (3, 5). Isoforms of 211 and 244 aa appear to lack transmembrane sequences. These and other isoforms of 491, 437, 322, 283 and 184 aa have alternate N- or C-termini, or lack an internal sequence (aa 268 - 296). The mature human IL-28 R alpha ECD shares 67%, 66%, 78% and 74% aa sequence identity with mouse, rat, canine and bovine IL-28 R alpha, respectively. Some cross-species reactivity has been shown (6). IL-28 R is constitutively expressed in most tissues, but its ligands are mainly produced by antigen presenting cells in response to viruses and their products (2 - 6). Signaling through IL-28 R alpha is similar to that of receptors for type I IFNs, including tyrosine phosphorylation, activation of JAK tyrosine kinases, STAT phosphorylation and formation of the IFN-stimulated gene factor 3 (ISGF-3) transcription factor complex (1 - 7). This signaling pathway induces antiviral activity and upregulates MHC class I antigen expression (2 - 7). Anti-proliferative activity has also been shown for IL-28/IL-28 R (7).