Converting IL-15 to a superagonist by binding to soluble IL-15Rα
Converting IL-15 to a superagonist by binding to soluble IL-15Rα
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DOI：
10.1073/pnas.0600240103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Sprent, Jonathan
中科院分区：
文献类型：
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作者：
Rubinstein, Mark P.;Kovar, Marek;Sprent, Jonathan
IL-15 通常在体内呈递为与 IL-15R α 结合的细胞相关细胞因子。我们在此表明，与重组可溶性 IL-15R α 相互作用后，可溶性 IL-15 的生物活性大大提高；注射后，可溶性 IL-15/IL-15R α 复合物迅速诱导记忆表型 CD8(+) 细胞和自然杀伤细胞的强烈选择性扩增。这些发现意味着 IL-15R α 与 IL-15 的结合可能会产生构象变化，从而增强 T 细胞上 β γ(c) 受体对 IL-15 的识别。 IL-15R α 结合的增强作用可以解释为什么 IL-15 通常充当细胞相关细胞因子。值得注意的是，IL-2（一种可溶性细胞因子）的结果有很大不同。因此，IL-2 功能通过与可溶性 IL-2R α 结合而受到显着抑制。
IL-15 is normally presented in vivo as a cell-associated cytokine bound to IL-15R alpha. We show here that the biological activity of soluble IL-15 is much improved after interaction with recombinant soluble IL-15R alpha; after injection, soluble IL-15/IL-15R alpha complexes rapidly induce strong and selective expansion of memory-phenotype CD8(+) cells and natural killer cells. These findings imply that binding of IL-15R alpha to IL-15 may create a conformational change that potentiates IL-15 recognition by the beta gamma(c) receptor on T cells. The enhancing effect of IL-15R alpha binding may explain why IL-15 normally functions as a cell-associated cytokine. Significantly, the results with IL-2, a soluble cytokine, are quite different; thus, IL-2 function is markedly inhibited by binding to soluble IL-2R alpha.