Interleukin-2, interleukin-15, and their receptors

Abstract

Both IL-15 and IL-2 are 14-15 kDa members of the four alpha-helical bundle family of cytokines that have T cell growth factor activity. In contrast to the pattern manifested by IL-2, IL-15 mRNA is produced by a wide variety of tissues other than T cells. We have demonstrated that IL-15 expression is posttranscriptionally regulated by multiple elements, including the ten upstream AUGs of the 5' UTR, a 48aa signal peptide and the carboxy-terminus of the mature protein. IL-15 utilizes two distinct receptor signaling pathways. In T cells the IL-15 receptor includes IL-2R beta and gamma c subunits shared with IL-2 as well as an IL-15 specific receptor, IL-15R alpha. However, mast cells respond to IL-15 using a receptor system that does not share elements with the IL-2R system but involves a novel 60-65 kDa IL-15RX subunit. In mast cells, IL-15 signaling involves JAK-2 and STAT-5 activation rather than the JAK-1 and JAK-3 as well as the STAT-3 and STAT-5 used by both IL-2 and IL-15 in activated T cells.