Recombinant Human IL-15R alpha Fc Chimera Protein, CF

Interleukin 15 Receptor alpha (IL‑15 R), also known as CD215, is a widely expressed 60 kDa transmembrane glycoprotein that plays an important role in the homeostasis and activation of NK cells and CD8⁺ memory T cells and participates in the development and function of many other hematopoietic cell types and non‑immune cell types (1 ‑ 3). Mature human IL‑15 R alpha consists of a 175 aa extracellular domain (ECD) containing one N‑linked glycosylation site, a 23 aa transmembrane segment, and a 39 aa cytoplasmic tail (4). Within the ECD, human IL‑15 R alpha shares approximately 60% aa sequence identity with mouse and rat IL‑15 R alpha. Alternate splicing of human IL‑15 R alpha generates additional isoforms with variable length deletions in the ECD and/or substitutions in the cytoplasmic domain (4, 5). IL‑15 R alpha binds to Interleukin‑15 with high affinity (6). IL‑15 additionally interacts with lower affinity to a complex of IL‑2 R beta and the common gamma chain ( gammac) which are also subunits of the IL‑2 receptor complex (7, 8). The use of shared receptor components contributes to the overlapping biological effects of IL‑15 and IL‑2. The dominant mechanism of IL‑15 action is known as transpresentation in which IL‑15/IL‑15 R alpha complexes are expressed on the surface of one cell and interact with complexes of IL‑2 R beta/ gammac on adjacent cells (9). This enables cells to respond to IL‑15 even if they do not express IL‑15 R alpha (10 ‑ 12). IL‑15/IL‑15 R alpha complexes can transmit reverse signaling that promotes cellular adhesion, tyrosine phosphorylation of intracellular proteins, and cytokine secretion by the IL‑15/IL‑15 R alpha expressing cells (13, 14). Shed soluble forms of IL‑15 R alpha retain the ability to bind tightly to IL‑15 and can inhibit IL‑15 bioactivity (6, 15, 16).