RECEPTOR MEDIATED T AND B CELL ACTIVATION

受体介导的 T 细胞和 B 细胞激活

• 批准号: 3774397
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3774397
• 关键词: AIDS; B lymphocyte; CD3 molecule; T cell receptor; antigen presenting cell; antireceptor antibody; calcium flux; crosslink; helper T lymphocyte; histocompatibility antigens; immunoglobulins; interleukin 2; laboratory mouse; leukocyte activation /transformation; lymphocyte proliferation; murine leukemia virus; phosphatidylinositols; phosphorylation; receptor coupling

The effect of prior activation history on subsequent responses of cloned T helper 1 (Th1) cells to TCR-mediated stimuli was examined. Th1 cells were maintained by stimulation with IL2 alone or by stimulation with specific antigen and APC in addition to IL2. Cells carried under both conditions proliferated equivalently in response to anti-CD3 antibody. However, anti-CD3 induced strong phosphatidyl inositol (PI) hydrolysis and increased [Ca++]i only in cells that had been maintained by stimulation with IL2 alone; cells that had been stimulated with specific antigen + APC gave neither PI nor Ca++ responses. The signaling pathways utilized by Th1 cells were thus influenced by prior stimulation through the TCR. 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 crosslinking were further analyzed by examining protein tyrosine phosphorylation induce 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.

先前的激活历史对克隆细胞随后反应的影响 检测辅助性T细胞1（Th 1）对TCR介导的刺激的反应。 th 1细胞 通过单独用IL 2刺激或通过用 特异性抗原和APC。 细胞在两个 条件增殖等同于对抗CD 3抗体的应答。 然而，抗CD 3诱导强烈的磷脂酰肌醇（PI）水解， 仅在刺激维持的细胞中增加[Ca++]i 单独IL 2;用特异性抗原+ APC刺激的细胞 没有PI和Ca++反应。 利用的信号通路 因此，Th 1细胞通过TCR受到先前刺激的影响。 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和sIg交联的增殖反应 尽管表达正常， 大多数T和B细胞对这些受体的表面水平。 分析早期 在这些细胞中的信号传导事件中，[Ca 2 +]i响应于 表面受体交联。 T和B的[Ca 2 +]i反应 来自MAIDS感染小鼠的细胞减少。 B细胞对sIg的应答 通过检测蛋白酪氨酸， 由sIg交联诱导磷酸化。 结果发现， 病毒感染时，选择性酪氨酸 磷酸化事件与其他事件的保守性。 响应 因此，来自MAIDS小鼠的B细胞的缺陷反映在选择的 酪氨酸磷酸化的改变对sIg信号的响应。