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  • 學位論文

探討介白素15受器alpha鏈細胞內區域結合分子

Identification of molecules interacting with IL-15 receptor alpha chain intracellular domain

指導教授 : 廖南詩 呂思潔
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摘要


介白素十五受器(interleukin 15 receptor; IL-15R)是由a、b 和g 鏈所組成,其中的b和g鏈為IL-15R與IL-2R所共用,而兩種受器各擁有其獨特的a鏈。IL-15與IL-15Ra鏈或與IL-15Rabg複合體的結合具有高親和性 (Ka = 1x1011)。由於 IL-15R與IL-2R共用b和g鏈,在體外的實驗發現,這兩種細胞激素對數種白血球之生長及活性有相同的影響;然而缺乏IL-15或IL-15Ra小鼠和缺乏IL-2或IL-2Ra小鼠卻有明顯不同的表現型。IL-15-/-及IL-15Ra-/-小鼠的自然殺手細胞、自然殺手T細胞、CD8aa+小腸上皮細胞間隙淋巴球以及CD8+T 細胞數目減少,而IL-2-/-及IL-2Ra-/-小鼠則沒有這些表現型。這些相異處可能由兩種受器使用不同的a鏈。有研究報告指出,IL-15Ra的細胞內區域(intracellular domain; IC domain)會和一些訊息傳導分子結合進而調控訊息反應 。我們實驗室先前用酵母菌雙雜交篩選方法,試圖找出與IL-15Ra之IC domain結合的分子。在這篇論文中,我以共同免疫沈澱法,在293T細胞株中,確認IL-15Ra是否會與這些由酵母菌雙雜交篩選出的分子結合。

並列摘要


IL-15 receptor consists of a, b and g chains. b and g are shared by IL-2R, while the IL-15Ra is unique. IL-15 binds to IL-15Ra chain alone with high affinity (Ka = 1x1011 M). Due to the b and g chains, IL-2 and IL-15 cytokines stimulate similar biological responses in vitro, and the characterizations of mice deficient in the IL-2/IL-2Ra or IL-15/IL-15Ra have revealed that these cytokines have markedly dissimilar functions in vivo. Therefore, differences in cellular responses to IL-2 or IL-15 likely result from the function of the distinct IL-2Ra and IL-15Ra. It has been reported that IL-15Ra associate with intracellular (IC) signaling molecules, and the IC domain of IL-15Ra may thus be involved in IL-15-induced signal transduction. Our lab identified molecules that interact with IL-15Ra IC domain by yeast-two hybrid screening. This thesis aims to confirm the interaction between IL-15Ra and the candidate molecules in the 293T cells by co-immunoprecipitation.

並列關鍵字

IL-15 receptor alpha chain

參考文獻


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