Molecular mechanisms of immune regulation.

免疫调节的分子机制。

• 批准号: 05272104
• 负责人: SASAZUKI Takehiko
• 金额: $ 158.14万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05272104/
• 关键词: HLA; antigenic peptide; TCR; prosessing; proteosome; トランスジェニックマウス; γδ型T細胞; アポトーシス; プロテオゾーム; 免疫制御; ペプチド; T細胞レパトワ; サイトカイン

To elucidate the molecular mechanisms of immune regulation in immune response to natural antigens in individuals, we investigated the recognition of HLA/peptide complexes by TCRs and the resultant cytokine expressions induced by interaction with the TCR.1.We elucidated the immune regulation by HLA-class I and Class II molecules by examining the genetic association between immune responses and HLA.2.We identified allergenic peptides that bind to HLA molecules and found that IgE production is inhibited by catepsin B.3.We elucidated the differences in HLA A bound motifs between alleles that are or are not associated with high frequencies of autoimmune disease susceptibility.4.We established monoclonal antibodies against a monocyte-specific antigen encoded by a gene that maps to the HLA region.5.We cloned proteosome and associated genes which are involved in the production of antigenic peptides.6.We found that Valpha14 TCR is necessary for NKT cell differentiation.7.We found new aspects of the relationship between gammadeltaT cell proliferation and GvH reactions.8.We found different transcription factors are used for Th1 and Th2 cytokine genes expression.9.We found a new soluble factor involved in the suppression of antibody production.

为了阐明个体对天然抗原免疫反应中免疫调节的分子机制，我们研究了tcr对HLA/肽复合物的识别以及与tcr相互作用诱导的细胞因子表达。我们通过检测免疫应答与hla - 2的遗传关联，阐明了hla - 1类和hla - 2类分子的免疫调节作用。我们发现了与HLA分子结合的致敏肽，并发现IgE的产生受到catepsin b3的抑制。我们阐明了与自身免疫性疾病易感性高频率相关或不相关的等位基因之间HLA A结合基序的差异。我们建立了针对一种单核细胞特异性抗原的单克隆抗体，该抗原由一种映射到HLA区域的基因编码。我们克隆了参与产生抗原肽的蛋白体和相关基因。我们发现Valpha14 TCR是NKT细胞分化所必需的。我们发现了γ - elat细胞增殖与GvH反应之间关系的新方面。我们发现不同的转录因子用于Th1和Th2细胞因子基因的表达。我们发现了一种新的可溶性因子参与抑制抗体的产生。

项目成果

Altmann D.M.: "The T cell respnse of HLA-DR transgenic mice to myelin basic protein and other antigens in the presence and absence of human CD4" J.Exp.Med.181. 867-875 (1995)

Altmann D.M.：“在存在和不存在人类 CD4 的情况下，HLA-DR 转基因小鼠的 T 细胞对髓磷脂碱性蛋白和其他抗原的反应”J.Exp.Med.181。

Adachi Y., et al.: "Positive selection of invariant V 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow derived cells." Proc.Natl.Acad.Sci.USA. 92. 1200-1204 (1995)

Adachi Y. 等人：“通过在骨髓来源细胞上表达的非主要组织相容性复合物编码的 I 类分子对不变 V 14 T 细胞进行正向选择。”

MaSuda E.S., et al.: "NFATx : a functional member of the NFAT family that is predominantly expressed in the thymus." Mol.Cell.Biol.15. 2697-2706 (1995)

MaSuda E.S. 等人：“NFATx：NFAT 家族的功能成员，主要在胸腺中表达。”

Watanabe S., et al.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells : analyzes of receptor signals for replication and transcription." J.Biol.Chem.270. 9615-9621 (1995)

Watanabe S.等人：“造血细胞中多瘤病毒复制子的粒细胞-巨噬细胞集落刺激因子依赖性复制：复制和转录的受体信号分析。”

Nishimura H.: "IL-15 is a novel growth factor for murine T cells induced by Salmonella infection" J. Immunol.(in press).

Nishimura H.：“IL-15 是沙门氏菌感染诱导的小鼠 T 细胞的新型生长因子”J.Immunol.（出版中）。