Altered Glycolipid Ligands for Va14i NKT cells

Va14i NKT 细胞的糖脂配体发生改变

• 批准号: 7080427
• 负责人: BARBARA A SULLIVAN
• 金额: $ 5.04万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7080427
• 关键词: CD1 molecule; T cell receptor; antigens; biological signal transduction; cell proliferation; cellular immunity; cytokine; gene expression; genetically modified animals; glycolipids; helper T lymphocyte; immunopharmacology; inhibitor /antagonist; interferon gamma; interleukin 4; laboratory mouse; leukocyte activation /transformation; ligands; natural killer cells; postdoctoral investigator; protein tyrosine kinase; receptor binding; stimulant /agonist; surface plasmon resonance; tissue /cell culture

DESCRIPTION (provided by applicant): Va14i NKT cells are a lymphocyte population that express an invariant Va14-Ja18 T cell antigen receptor (TCR). These cells are reactive to the CD1d (a nonclassical class I antigen presenting molecule) when CD1d binds the marine sponge-derived glycolipid a-galactosyl-ceramide (aGalCer). When activated, Va14i cells rapidly produce large amounts of IFNg and IL-4. In the proposed experiments, we will identify novel lipoglycan antigens that can stimulate Va14i NKT cells in different ways, including antagonists and antigens that alter the pattern of NKT cell cytokine production. We will determine the affinity of the interaction between the Va14i TCR and CD1 when bound to glycolipid variants and determine if the hierarchy of affinities is related to antigenic potency and cytokine profile. We will also test the physiologic consequence of differential signal strength in Va14i T cell development via antigenic challenge of mature Va14i T cells by altering the expression of fyn or Ick tyrosine kinases. The proposed experiments will provide strategies for the augmentation and regulation of this important subset of T lymphocytes.

描述（由申请方提供）：Va 14 i NKT细胞是表达不变Va 14-Ja 18 T细胞抗原受体（TCR）的淋巴细胞群。当CD 1d结合海洋海绵衍生的糖脂α-半乳糖基神经酰胺（aGalCer）时，这些细胞对CD 1d（一种非经典的I类抗原呈递分子）具有反应性。当激活时，Va 14 i细胞迅速产生大量IFNg和IL-4。在拟议的实验中，我们将确定新的脂聚糖抗原，可以刺激Va 14 i NKT细胞以不同的方式，包括拮抗剂和抗原，改变NKT细胞的细胞因子的生产模式。我们将确定Va 14 i TCR与CD 1结合糖脂变体时相互作用的亲和力，并确定亲和力等级是否与抗原效力和细胞因子谱相关。我们还将通过改变fyn或Ick酪氨酸激酶的表达，通过成熟Va 14 i T细胞的抗原攻击，测试Va 14 i T细胞发育中差异信号强度的生理后果。拟议的实验将提供策略的增强和调节这一重要的T淋巴细胞亚群。