Recombinant Feline IL-12 Protein

Interleukin 12 (IL-12) is a 75 kDa heterodimeric glycoprotein that is composed of the disulfide-linked 35 kDa (p35) and 40 kDa (p40) subunits. Whereas p35 is an alpha-helical protein related to IL-6, the p40 subunit belongs to the type I cytokine receptor family. The feline IL-12 p35 gene encodes a 222 amino acids (aa) precursor protein with a 25 aa signal peptide. Mature feline p35 contains four potential N-linked glycosylation sites and one intrachain disulfide bond. p35 is synthesized constitutively but can be upregulated by the class II MHC-TCR interaction. p35 is never secreted unbound to p40. Mature feline p35 shows 91%, 88%, 86%, 57%, 56% and 75% aa identity with canine, human, porcine, rat, mouse and guinea pig p35, respectively. The feline p40 gene encodes a secreted 329 aa precursor protein with a 22 aa signal peptide. Mature feline p40 contains one fibronectin type III and one Ig C2-like domain. It is known to exist as a monomer, a homodimer, and as heterodimers linked either to p35 to form IL-12, or to p19 to create IL-23. p40 synthesis is upregulated by many different inflammatory signals including LPS and CpG. Mature feline p40 shows 94%, 85%, 85%, 67%, 67% and 76% aa identity to canine, human, porcine, rat, mouse and guinea pig p40, respectively. Cells known to produce IL-12 include macrophages, dendritic cells, monocytes, Langerhans cells, neutrophils, and keratinocytes. The signaling receptor for IL-12 is composed of two type I transmembrane glycoproteins belonging to the type I cytokine receptor superfamily. IL-12 receptor beta1 (IL-12 R beta1) is 100 kDa protein that serves as the principal binding site for the p40 subunit. IL-12 receptor beta2 (IL-12 R beta2) is 130 kDa protein that interacts primarily with p35 and functions as the signal transducing component. IL-12 facilitates hematopoietic stem cell proliferation, induces NK cell proliferation, promotes IgG production (in mice), and potentiates the expansion and late activation of Th1 CD4⁺ T cells (1 - 5).