Pattern recognition by human γδ T cells and innate immunity.

人类 γδ T 细胞的模式识别和先天免疫。

• 批准号: 12670299
• 负责人: TANAKA Yoshimasa
• 金额: $ 2.18万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670299/
• 关键词: immune system; γδ T cell; nonpeptide antigen; T cell receptor; pathogenic microbe; innate immunity; acquired_immunity; tumor cell; ピロリン酸モノエステル; アルキルアミン; 結核菌; 病原性大腸菌; パターン抗原; 非ペプチド抗原; パターン認識

Innate immunity and acquired immunity play an essential role in human immune system, in which the former system recognize pathogen-associated molecular patterns and the latter non-self peptide antigens. The representative cells are macrophages and αβ T cells, respectively. Although human γδ T cells are considered to be involved in innate immunity since they recognize pyrophosphomonoesters and alkyl amines derived from pathogenic microbes, they are, on their other hand, classified as a member of acquired immunity based on their cell surface receptor generated as a result of gene rearrangement. In this study, immunological nature of human γδ T cells was elucidated by examining their recognition mechanism of nonpeptide antigens. Nitrogen-containing bisphosphonate was used in the present study. In the primary reaction, cell aggregation and interferon-γ Production were dependent on the existence of macrophage-lineage cells, indicating that antigen-presenting cells are involved in the recognition of nonpeptide antigens by γδ T cells. In addition, tumor cells were demonstrated to be able to present nonpeptide antigens to human γδ T cells in the secondary reaction. In order to elucidate the precise recognition mechanism of nonpeptide antigens by γδ T cell receptors, gene transfer system using a TCR-negative Jurkat cell line was employed, in which germline-encoded lysine residues in Jγ1.2 segment were shown to be involved in the interaction. This indicates that canonical sequence of γδ T cell receptors recognizes directly nonpeptide antigens, while γδ T cell receptors undergo gene rearrangement. Taken, together, human γδ T cells were confirmed to have two distinct characters, innate immunity and acquired immunity, on the basis of their mechanism for antigen recognition.

天然免疫和获得性免疫在人体免疫系统中起着重要的作用，前者识别病原体相关的分子模式，后者识别非自身多肽抗原。代表性细胞分别是巨噬细胞和αβ T细胞。虽然人γδ T细胞被认为参与先天免疫，因为它们识别来源于病原微生物的焦磷酸单酯和烷基胺，但另一方面，它们基于其作为基因重排的结果产生的细胞表面受体被分类为获得性免疫的成员。本研究通过检测人γδ T细胞对非肽类抗原的识别机制，阐明了人γδ T细胞的免疫学特性。在本研究中使用含氮双膦酸盐。在初级反应中，细胞聚集和γ-干扰素的产生依赖于巨噬细胞系细胞的存在，表明抗原呈递细胞参与γδ T细胞对非肽类抗原的识别。此外，肿瘤细胞被证明能够在二次反应中向人γδ T细胞呈递非肽抗原。为了阐明γδ T细胞受体对非肽类抗原的精确识别机制，采用TCR阴性的Jurkat细胞系进行基因转移，发现Jγ1.2片段中的种系编码赖氨酸残基参与了相互作用。这表明γδ T细胞受体的典型序列直接识别非肽类抗原，而γδ T细胞受体则经历基因重排。综上所述，基于其抗原识别机制，人γδ T细胞被证实具有两种不同的特性，即天然免疫和获得性免疫。

项目成果

Yu Kato, Yoshimasa Tanaka, Fumi Miyagawa, Seiji Yamashita, and Nagahiro Minato: "Targeting of tumor cells for human γδ T cells by nonpeptide antigens"The Journal of Immunology. 167. 5092-5098 (2001)

Yu Kato、Yoshimasa Tanaka、Fumi Miyakawa、Seiji Yamashita 和 Nagahiro Minato：“非肽抗原靶向人类 γδ T 细胞的肿瘤细胞”免疫学杂志 167. 5092-5098 (2001)。

Craig T. Morita, Hoi K. Lee, Hong Wang, Hongmin Li, Roy A. Mariuzza, and Yoshimasa Tanaka: "Structural features of nonpeptide prenyl pyrophosphates that determine their antigenicity for human γδ T cells"The Journal of Immunology. 167. 36-41 (2001)

Craig T. Morita、Hoi K. Lee、Hong Wang、Hongmin Li、Roy A. Mariuzza 和 Yoshimasa Tanaka：“非肽异戊二烯焦磷酸的结构特征决定其对人类 γδ T 细胞的抗原性”《免疫学杂志》167。 36。 -41 (2001)

Hiroyuki Nishimura, Taku Okazaki, Yoshimasa Tanaka, Kazuki Nakatani, Masatake Hara, Akira, Matsumori, Shigetake Sasayama, Akira Mizoguchi, Hiroshi Hiai, Nagahiro Minato, and Tasuku Honjo: "Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice"

Hiroyuki Nishimura、Taku Okazaki、Yoshimasa Tanaka、Kazuki Nakatani、Masatake Hara、Akira、Matsumori、Shigetake Sasayama、Akira Mizoguchi、Hiroshi Hiai、Nagahiro Minato 和 Tasuku Honjo：“PD-1 受体缺陷型小鼠的自身免疫性扩张型心肌病”

Hirohito Kobayashi, Yoshimasa Tanaka, Junji Yagi, Hiroshi Toma, Takehiko Uchiyama: "Gamma/delta T cells provide innate immunity against renal cell carcinoma"Cancer Immunology and Immunotherapy. 50. 115-124 (2001)

Hirohito Kobayashi、Yoshimasa Tanaka、Junji Yagi、Hiroshi Toma、Takehiko Uchiyama：“γ/δ T 细胞提供针对肾细胞癌的先天免疫”癌症免疫学和免疫治疗。

Seigo Korematsu, Yoshimasa Tanaka, Susumu Hosoi, Satoshi Koyanagi, Toyokazu Yokota, Bunzo Mikami, Nagahiro Minato: "C8/119S mutation of major mite allergen Derf-2 leads to degenerate secondary structure and molecular polymerization and induces potent and

Seigo Korematsu、Yoshimasa Tanaka、Susumu Hosoi、Satoshi Koyanagi、Toyokazu Yokota、Bunzo Mikami、Nagahiro Minato：“主要螨过敏原 Derf-2 的 C8/119S 突变导致二级结构和分子聚合的简并，并诱导有效和