IL-15, a novel T cell growth factor that shares activities and receptor components with IL-2

Interleukin 15 is a newly discovered cytokine that shares biological activities with IL-2 and, like IL-2, is a member of the four-helix bundle cytokine family. We have shown that IL-15 shares components of the receptor for IL-2: the alpha chain of the IL-2R is not required, but both the beta and gamma chains are needed for IL-15 mediated bioactivities. A defect in IL-15 signaling may therefore contribute to the phenotype of X-linked severe combined immunodeficiency in humans, resulting from mutations in the common gamma chain. Differential ability of cells to bind and respond to IL-2 and IL-15 suggested the existence of an additional IL-15 specific receptor component. We identified an IL-15 specific binding protein (IL-15R alpha) on a murine T cell and isolated the corresponding cDNA. The IL-15R alpha is not a member of the hematopoietin receptor superfamily, but is structurally related to the alpha chain of the IL-2R. Differences in the expression pattern of IL-15 and its receptor compared to the IL-2 system suggest unique in vivo roles for IL-15.