Volume 4, Issue 4, Pages 329-336 (April 1996) IL-15: A Pleiotropic Cytokine with Diverse Receptor/Signaling Pathways Whose Expression Is Controlled at Multiple Levels  Yutaka Tagaya, Richard N Bamford, Andrew P DeFilippis, Thomas A Waldmann  Immunity  Volume 4, Issue 4, Pages 329-336 (April 1996) DOI: 10.1016/S1074-7613(00)80246-0

Figure 1 Ribbon Diagram Showing Structural Features Common to the Four α Helix Bundle Cytokine Family The four helices are designated A, B, C, and D. The up–up–down–down topology refers to the fact that helices A and B point up, while helices C and D point down. (Figure reproduced with permission from Rozwarski et al. 1994, Current Biology 2 159–173). Immunity 1996 4, 329-336DOI: (10.1016/S1074-7613(00)80246-0)

Figure 2 Diagram of Two IL-15 Receptor/Signaling Systems (A) The T cell IL-15R includes IL-15Rα, IL-2/IL-15Rβ, and γc subunits. The signal transduction pathway of this multisubunit receptor involves the activation of Jak1 and Jak3 as well as the tyrosine phosphorylation and nuclear translocation of Stat3 and Stat5. (B) The mast cell IL-15R does not involve known components of the T cell IL-15R system. However, mast cells express a novel 60–65 kDa IL-15R, provisionally designated IL-15RX. The membrane proximal events of IL-15 signal transduction involve Jak2 and Stat5 instead of the Jak1/Jak3 and Stat3/Stat5 that are utilized by T cells. Immunity 1996 4, 329-336DOI: (10.1016/S1074-7613(00)80246-0)

Figure 3 Model Defining the Putative Mechanism Underlying the Expression of HTLV-1-R/IL-15 Fusion Message in the Adult T Cell Leukemia Cell Line HuT-102 (A) The 5′ region of many HTLV-1 transcripts consists of a 118 nt element that originates at the cap site of the R region of the virus. This element of the R region that is the common splice component of HTLV-1 tax, env, and other HTLV-1 transcripts represents the most 5′ 118 nt of the UTR of these messages. (B) The predominant IL-15 message produced by HuT-102 is a chimeric mRNA joining 118 nt of the R region of the long terminal repeat of HTLV-1 and the 5′ UTR of IL-15. The genomic structure of human IL-15 shown is deduced from the murine genomic architecture (Anderson et al. 1995a). Immunity 1996 4, 329-336DOI: (10.1016/S1074-7613(00)80246-0)

Figure 4 5′ UTR Sequence of Human IL-15 from Normal Cells and HuT-102 (A) 5′ UTR of IL-15 as reported (Grabstein et al. 1994) contains ten double underlined ATGs (red) upstream of the initiation ATG, which is shown in green. (B) The sequence of the 5′ UTR of HTLV-1-R/IL-15 fusion cDNA found in HuT-102. The underlined blue element identifies the 118 nt common splice sequence from the HTLV-1-R region. Positions 215 and 227 are splice-acceptor sites for R and the double underlined ATGs (red) are upstream of the initiation ATG that is shown in green. Numbers at right correspond to those of wild-type IL-15 5′ UTR (Figure reproduced with permission from Bamford et al. 1996, Proc. Natl. Acad. Sci. USA, in press). Immunity 1996 4, 329-336DOI: (10.1016/S1074-7613(00)80246-0)