CD8+ T CELL RECOGNITION OF TH1 AND TH2

CD8 T 细胞对 TH1 和 TH2 的识别

基本信息

批准号：
6511062
负责人：
HONG JIANG
金额：
$ 25.63万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-03-01 至 2004-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6511062
关键词：
MHC class I antigen Retroviridae T cell receptor cell cell interaction cell differentiation cytotoxic T lymphocyte gene expression helper T lymphocyte hybridomas interleukin 2 laboratory mouse laboratory rabbit leukocyte activation /transformation tissue /cell culture transfection

项目摘要

CD4+ TH1 and TH2 cells differ in several ways. They secrete different cytokines. The express different cell surface molecules and different transcription factors. These different molecules expressed by TH1 and TH2 contribute to their unique functions and to mechanisms that specifically regulate the growth and differentiation of the subsets. We have recently identified a new functional difference between TH1 and TH2 cells. As part of a series of studies to understand better how CD8+ T cells regulate CD4+ T cell responses, we identified a CD8+ T cell response that was Qa-1-restricted and VBeta8-specific and we cloned CD8+ T cell hybridomas with the specificity. These hybridomas respond to TH1 cells and to a lymphoma that express VBeta8 TCR and Qa-1a but not to VBeta8+ Qa-1b+ cells. The hybridomas, however, do not respond to Qa-1a+ VBeta8+ TH2 cells. This is true even for paris of TH1 and TH2 cells that express identical TCRBeta chains. This difference is not due to an affect of cytokines or other products secreted by the CD4+ cells during the time period examined. The data instead suggest that TH1 and TH2 cells differ either in antigen processing or in the expression of cell surface molecules important in T-T interactions. Consistent with this, the difference between TH1 and TH2 cells is preserved after fixation of the CD4+ cells. In this proposal, we will determine the molecular difference(s) between TH1 and TH2 cells that account(s) for their differential ability to be recognized by antigen-specific CD8+ T cells. We will determine when during TH subset differentiation this difference emerges. We will determine if this difference uniquely applies to the recognition of TCR peptide presented by Qa-1 or if CD8+ T cells specific for other peptides presented by MHC class I molecules also distinguish between TH1 and TH2 targets.

CD4+ Th1和Th2细胞在几种方面有所不同。他们分泌不同的细胞因子。表示不同的细胞表面分子和不同的转录因子。这些不同的分子由Th1和 TH2有助于其独特的功能和机制特别调节亚集的生长和分化。我们最近确定了TH1和 Th2细胞。作为一系列研究的一部分，以更好地了解CD8+如何 T细胞调节CD4+ T细胞响应，我们确定了CD8+ T细胞响应是QA-1限制的和特定于VBETA8的响应，我们克隆了CD8+ 具有特异性的T细胞杂交瘤。这些杂交瘤对TH1做出了反应细胞和表达VBETA8 TCR和QA-1A的淋巴瘤，但不能 VBETA8+ QA-1B+细胞。但是，杂交瘤不对QA-1A+响应 VBETA8+ Th2细胞。即使对于Th1和Th2细胞的巴黎，这也是如此表示相同的TCRBETA链。这种差异不是由于在CD4+细胞分泌的细胞因子或其他产品的影响检查的时间段。相反，数据表明TH1和TH2 细胞在抗原加工或细胞的表达上有所不同表面分子在T-T相互作用中很重要。与此一致固定后，Th1和Th2细胞之间的差异被保留 CD4+细胞。在此提案中，我们将确定分子 th1和Th2细胞之间的差异通过抗原特异性CD8+ T细胞识别的差异能力。我们将确定何时在二次区分期间此差异出现。我们将确定这种差异是否唯一适用于识别QA-1或CD8+ T细胞特有的TCR肽的识别对于MHC I类分子提出的其他肽也有区别在Th1和Th2目标之间。