Human interleukin 15 (IL-15) is a protein of 114 amino acids after cleavage of a 48 amino acid signal peptide. An alternative splice form of IL-15 has also been identified with an identical mature sequence, but a shorter signal sequence. Interestingly, the shorter prepeptide is not secreted and may represent a functional intracellular molecule. In addition, a membrane-bound form of IL-15 has also been reported, which may be an important physiological form of the molecule. Human IL-15 has 97% and 73% amino acid sequence identity with simian and mouse IL-15, respectively. Both human and simian IL-15s are active on mouse cells. IL-15 is a novel cytokine that shares many biological properties with IL-2. Originally identified in media conditioned by a monkey kidney epithelial cell line (CVI/EBNA) based on its mitogenic activity on the mouse T cell line (CTLL-2), IL-15 was independently discovered as a cytokine produced by a human adult T-cell leukemia cell line (HuT-102) that stimulated T cell proliferation and was designated IL-T . High-affinity cell surface receptors for IL-15 have been detected on a variety of cells including T cells, B cells, and NK cells as well as on non-lymphoid cells. The IL-15 receptor is composed of three molecules; an IL-15 specific α-chain of 237 amino acids, plus a β-chain and γ-chain that is shared by the receptor system for IL-2. The α-chain binds IL-15 with high affinity. It shows 54% amino acid sequence identity with mouse IL-15 R and exists in multiple alternatively spliced forms. Although the IL-15 receptor is composed of 3 chains, IL-15 will signal through a dimer and the βγ-chain itself may have multiple functions. IL-15 has biological activities similar to IL-2 and has been shown to stimulate the growth of natural killer cells, activated peripheral blood T lymphocytes, tumor infiltrating lymphocytes (TILs), and B cells. In addition, IL-15 has also been shown to be a chemoattractant for human blood T lymphocytes and to induce both lymphokine-activated killer (LAK) activity in NK cells and the generation of cytolytic effector cells. IL-15 apparently also has effects on cells not involved in immune responses. Skeletal muscle cells express IL-15 and IL-15 R mRNAs and respond to the addition of IL-15.