Interleukin 15 receptor alpha (IL-15 R alpha ) is a high affinity receptor that specifically binds IL-15 with high affinity and associates as a heterotrimer with the IL-2 receptors beta and gamma subunits to initiate signal transduction. IL-15 R alpha is expressed on a wide variety of T cells and B cells as well as non-lymphoid cells. IL‑15 R alpha is a 58-60 kDa protein that shares structural similarities to the IL-2 R alpha protein. IL-15 R alpha and IL-2 R alpha genes also share similar intron-exon organization and are closely linked on human chromosome 10p14-p15. Human IL-15 R alpha shares 45% amino acid (aa) homology with the mouse form of the receptor. Eight isoforms of IL‑15 R alpha mRNA have been identified resulting from alternative splicing events involving different exons. The exclusion of exon 2 results in an IL-15 R alpha isoform that does not bind IL-15. Human IL-15 R alpha DE3 cDNA encodes a 267 aa protein that contains a 30 aa signal sequence, a 175 aa extracellular region containing one N-linked glycosylation site, a 21 aa transmembrane domain and a 41 aa cytoplasmic tail. Signaling of IL-15 can occur in one of three ways; through the heterotrimeric complex of IL-15 R alpha, IL-2 R beta, and IL-2 R gamma _c, through the heterodimeric complex of IL-2 R beta and IL-2 R gamma _c,  or through a novel 60-65 kDa IL-15 RX subunit found on mast cells. The binding of IL-15 to IL-15 R alpha has been reported to antagonize the TNF-alpha -mediated apoptosis in fibroblasts by competing with TNF RI for TRAF2 binding.