Recombinant Human IL-7R alpha/CD127 Fc Chimera Protein, CF

Interleukin 7 Receptor alpha (IL-7 R alpha), also known as CD127, is a 75 kDa hematopoietin receptor superfamily member that plays an important role in lymphocyte differentiation, proliferation, and survival (1, 2). Mature human IL-7 R alpha consists of a 219 amino acid (aa) extracellular domain (ECD) with one fibronectin type-III domain and a WSXWS motif, a 25 aa transmembrane segment, and a 195 aa cytoplasmic domain (3). Alternate splicing of human IL-7 R alpha generates a secreted soluble form of the receptor (3). Within the ECD, human IL‑7 R alpha shares 67% aa sequence identity with mouse and rat IL-7 R alpha. IL-7 R alpha associates with the common gamma chain ( gamma_c) to form the functional high affinity IL-7 receptor complex (4). The gamma_c is also a subunit of the receptors for IL-2, -4, -9, -15, and -21. Human and mouse IL‑7 show cross-species activity through the IL-7 receptor (3, 5). IL-7 R alpha is expressed on double negative (CD4^-/CD8^-) and CD4⁺ or CD8⁺ single positive T cells as well as on CD8⁺ memory T cells and their precursors (6, 7). It is expressed early in B cell development, prior to the appearance of surface IgM (6). In mouse, IL-7 activation of IL-7 R alpha is critical for both T cell and B cell lineage development (8). In human, by contrast, it is required for T cell but not for B cell development (9). IL-7 induces the downregulation and shedding of cell surface IL‑7 R alpha (10). IL-7 R alpha additionally associates with TSLP R to form the functional receptor for thymic stromal lymphopoietin (11, 12). TSLP indirectly regulates T cell development by modulating dendritic cell activation (2, 13). Knockout of TSLP R in mice provokes minor changes in B and T cell development compared to those seen with IL-7 R alpha deletion (8, 14). The complexity of IL-7 R alpha biology is suggested by the competition between IL-7 and TSLP for receptor binding and by the ability of IL-7 R alpha to form functional complexes with SCF R and HGF R (11, 12, 15, 16).