がん抗原の発現調節と免疫系による認識

• 研究課題/領域番号: 01010012
• 研究種目: がん特別研究
• 配分区分: 補助金
• 研究機関: 千葉大学
• 研究代表者: 谷口 克 千葉大学, 医学部・高次機能制御研究センター, 教授 (80110310)
• 研究分担者: 横山 一成 理化学研究所, ジーンバンク室, 研究員 (80182707) ; 竹森 利忠 国立予防衛生研究所, 細胞免疫, 部長 (60114295) ; 成松 久 慶応大学, 医学部・微生物, 講師 (40129581) ; 松岡 雄治 福岡大学, 医学部・第一生化学, 教授 (70078773) ; 藤原 大美 大阪大学, 医学部・バイオメディカル教育研究センター, 助教授 (70116094)
• 研究期間 (年度): 1988 – 1990
• 研究課題ステータス: 完了 (1989年度)
• 配分額: 19,000千円 (直接経費: 19,000千円); 1989年度: 19,000千円 (直接経費: 19,000千円)
• キーワード: がん抗原 / がん遺伝子 / 分化抗原 / 糖転移酵素 / Antisense RNA

研究概要

がん遺伝子の活性化に伴って発現されるがん抗原の同定と免疫系による認識、発現機構の解明、支配遺伝子および関連遺伝子の解析を行なうことによって免疫系に重要ながん抗原の分子免疫学的研究を行い次の成果を得た。1.腫瘍抗原の同定:(1)ras遺伝子導入細胞およびメラノーマ細胞から免疫学的(T細胞が認識)に同定された抗原はhsp、内在性ウィルスenv蛋白等の内在性抗原であり、これらの一部は遺伝子クローニングに成功し、発現様式を解析した。がん遺伝子活性化によって通常では出現しない内在性抗原の発現が重要であることを示した。(2)精製src誘発がん抗原(60kd)を用いたAgーpulsedマクロファージで効率良く腫瘍抵抗性を誘導した。2.腫瘍関連抗原発現機序に関するもの:(1)NGAの新しい遺伝子ファミリーのcDNAクローン化に成功。膜での表現型はCEAと同様蛋白が脂質を介して結合していることが判明。(2)マウスβ1ー4ガラクトース転移酵素遺伝子(65kb)のcDNAおよびゲノムDNAクローン化に成功。遺伝子構造解析の結果Exon1、2、4、5、6、7を使用しExon6にUDPーgal結合部があることが判明。糖鎖抗原発現の分子メカニズム解明に貢献した。3.腫瘍化、脱腫瘍化に関与する遺伝子と腫瘍抗原の発現:(1)Antisenseーcーmycで誘導される74kd蛋白の精製に成功。一部アミノ酸配列を決定した。(2)核または細胞膜に局在する抗原分子のcDNAをクローン化するtag付ベクターを開発。がん遺伝子活性化から抗原発現までのカスケードの解析に有用。(3)幼若リンフォーマによる特異的に発現する遺伝子αcDNAクローン化に成功。

研究成果

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