Recombinant Mouse IL-17A/F Heterodimer Protein

IL-17A/F is an approximately 40 kDa, secreted, disulfide-linked heterodimeric glycoprotein comprised of two members of the IL-17 family of cytokines, IL-17A and IL-17F (1). Members of this family demonstrate a structural motif termed a cysteine-knot that also characterizes a large superfamily of growth factors. Although most cysteine-knot superfamily members use three intrachain disulfide bonds to create a knot, IL-17 family molecules generate the same structural form with only two disulfide links (2 - 4). Mouse IL-17A is synthesized as a 158 amino acid (aa) precursor that contains a 25 aa signal sequence and a 133 aa mature region. The mature chain contains one potential site of N-linked glycosylation. Mouse IL-17F is synthesized as a 161 aa precursor. Like IL-17A, IL-17F contains one potential site of N-linked glycosylation. IL-17A and IL-17F share 50% aa sequence identity. Mouse IL-17A and IL-17F are 61% and 56% identical to human IL-17A and IL-17F on the aa level, respectively. IL-17A/F and the IL-17A and IL-17F homodimers are produced by an activated subset of CD4⁺ T cells, termed Th17 (1, 5 - 7). IL-23 drives Th17 lymphocytes to produce these cytokines (5, 8 - 9). Studies have identified that the widely expressed receptors IL-17RA and IL-17RC form a heterodimer for the binding of IL-17A and IL-17F, and IL-17A/F (5, 10 - 12). IL-17A/F is a biologically active protein that induces chemokine production and airway neutrophilia with intermediate potency between IL-17A (most potent) and IL-17F (least potent) (6).