MOLECULAR AND FUNCTIONAL STUDIES OF TCA3

描述(根据申请者的抽象和具体目标改编)：完毕 在过去的八年里，这位研究人员分离到了一个表达在 抗原或有丝分裂原刺激的T细胞，鉴定为促炎因子 β-趋化因子家族的细胞因子，表明它可以在两个 形式：TCA3和P500，并且这两种形式的趋化活性不同 (中性粒细胞/单核细胞和单核/巨噬细胞)。这个基因是 克隆并定位到小鼠的11号染色体。此外，作为 试图研究这种趋化因子的生物活性，研究人员 发现转导TCA3的肿瘤细胞不能在同基因宿主中生长。 移植了这些肿瘤的动物对 肿瘤细胞(即使未转TCA3)。这些问题将会是 在本申请中提出的问题是：1.结构差异如何 在TCA3和P500中与其特异性的差异相对应 趋化活性？TCA3和P500是TCA3和P500的替代剪接产品 相同的基因，在氨基酸44之后有很大的差异(TCA3是69个氨基酸；P500 是61aa的长度)。2.哪些细胞类型有这些趋化因子的受体， 这些受体的生化结构是什么？3.什么是 肿瘤细胞产生TCA3抑制肿瘤生长的机制 产生肿瘤免疫的基础是什么？

DESCRIPTION (Adapted from Applicant's abstract and Specific Aims.): Over the last eight years, this investigator has isolated a cDNA expressed in antigen or mitogen-stimulated T-cells, identified it as a pro-inflammatory cytokine of the beta-chemokine family, shown that it can be expressed in two forms: TCA3 and P500, and that the two forms differ in chemotactic activity (neutrophil/monocyte and monocytes/macrophages, respectively). The gene was cloned and mapped to mouse chromosome 11. Furthermore, as part of an attempt to study the biological activity of this chemokine, the investigator found that TCA3-transfected tumor cells failed to grow in syngeneic hosts. Animals transplanted with these tumors achieved specific immunity to the tumor cells (even without transfection of TCA3). The questions that will be asked in the present application are: 1. How do the structural differences in TCA3 and P500 correspond to the differences in the specificity of their chemotactic activity? TCA3 and P500 are alternate splice products of the same gene and differ extensively after amino-acid 44 (TCA3 is 69 aa's; P500 is 61aa's long). 2. What cell-types have receptors for these chemokines, and what is the biochemical structure of those receptors? 3. What is the mechanism for the inhibition of tumor growth when tumor cells produce TCA3, and what is the basis of the tumor immunity that develops?