RECEPTOR MEDIATED T AND B CELL ACTIVATION

受体介导的 T 细胞和 B 细胞激活

• 批准号: 2463770
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2463770
• 关键词: B lymphocyte; T cell receptor; T lymphocyte; biological signal transduction; calcium flux; crosslink; laboratory mouse; leukocyte activation /transformation; lymphocyte proliferation; murine AIDSs; murine leukemia virus; phosphorylation; receptor binding; receptor expression

Receptor-mediated activation was analyzed in T and B lymphocytes from normal mice and from mice infected with the MAIDS-inducing defective murine leukemia virus. Several weeks after viral infection, the proliferative responses of T and B cells to cross-linking of TCR and sIg respectively were significantly reduced despite the expression of normal surface levels of these receptors by most T and B cells. To analyze early signaling events in these cells, [Ca2+]i was measured in response to surface receptor cross-linking. The [Ca2+]i responses of both T and B cells from MAIDS-infected mice were decreased. B cell responses to sIg cross-linking were further analyzed by examining protein tyrosine phosphorylation induced by sIg cross-linking. It was found that after virus infection, there was a progressive loss of selected tyrosine phosphorylation events with conservation of other events. The response defect in B cells from MAIDS mice is thus reflected in selected alterations of tyrosine phosphorylation in response to sIg signaling. Costimulatory B7 molecules (B7-1 or CD80; and B7-2 or CD86) are known to bind to T cell costimulatory receptors CD28 and CTLA4. Engagement of CD28 is know to transduce signals in T cells that play a critical role in T cell activation; however, little is known of the ability of B7 molecules to themselves act as signal transducing molecules. The effect of B7-1 and B7-2 crosslinking was assessed in the B cell lymphoma BAL.17. Initial studies demonstrated that B7 crosslinking induces AP-1 components including c-fos and c-jun, as demonstrated by gel retardation and "super-shift" assays. These findings indicate that B7 engagement by counter-receptors such as CD28 or CTLA4 may lead to bidirectional effects, functioning to transduce signals in B7-expressing cells such as B lymphocytes, in addition to signaling CD28/CTLA4 positive T cells.

受体介导的活化在T和B淋巴细胞中进行了分析， 正常小鼠和感染MAIDS诱导缺陷型 鼠白血病病毒 病毒感染后几周， T和B细胞对TCR交联的增殖反应， sIg分别显著降低，尽管表达 大多数T和B细胞的这些受体的正常表面水平。 到 分析这些细胞中的早期信号传导事件，测量[Ca 2 +]i， 对表面受体交联的反应。 [Ca 2 +]i反应 MAIDS感染小鼠的T和B细胞均减少。 B细胞 对sIg交联的反应进一步分析， 由sIg交联诱导的蛋白酪氨酸磷酸化。 这是 发现病毒感染后， 选择的酪氨酸磷酸化事件， 事件 因此，来自MAIDS小鼠的B细胞中的应答缺陷是 反映在酪氨酸磷酸化的选择性改变中， 对sIg信号的响应。 共刺激B7分子（B7-1或CD 80;和B7-2或CD 86）是已知的 与T细胞共刺激受体CD 28和CTLA 4结合。 接合 已知CD 28的表达可以抑制T细胞中的信号，这些信号在T细胞中起着关键的作用。 在T细胞活化中的作用;然而，很少有人知道的能力， B7分子本身充当信号转导分子。 的 在B细胞中评估B7-1和B7-2交联的作用 淋巴瘤BAL.17。 初步研究表明，B7交联 诱导AP-1组分，包括c-fos和c-jun，如 凝胶阻滞和“超位移”测定。 这些发现表明 B7与反受体如CD 28或CTLA 4的结合可能导致 双向效应，其功能是将信号 表达B7的细胞，如B淋巴细胞，除了信号传导外， CD 28/CTLA 4阳性T细胞。