MOLECULAR/CELLULAR BASIS OF CARDIAC ALLOGRAFT REJECTION

本研究建议的主要目标是确定 参与免疫识别过程的分子成分 同种异体移植排斥反应。 移植物排斥反应是由T细胞启动的， 受体通过克隆识别外来移植物的抗原， 表达的TCR。 这个认知过程的基础是 由TCR、MHC分子组成的三分子复合物（所述三分子复合物的 受体和/或供体类型），和代谢上来源于 处理过的移植物抗原 免疫过程中这种复合物的形成 对移植物的反应引发了一系列细胞内和细胞间的 导致移植物破坏的反应。 因此，澄清 三分子复合物的性质和随后的事件 不仅能拓宽我们对移植排斥反应的理解 排斥过程，但也可能提供一种手段，以诱导移植- 具体宽容。 该提案的具体目标包括： 1. 由分离自人的GIL的TCR库使用的表征 在不同的大鼠品系组合中进行心脏同种异体移植， 一系列组织相容性抗原。 2. 从具有特异性的GIL建立T细胞系和/或克隆 对移植物抗原的反应性及其在介导 过继移植后的心脏移植排斥反应 3.作为移植物靶点的移植物抗原的鉴定 反应性T细胞及其在排斥反应中的作用分析 反应

The primary objectives of this research proposal are to identify the molecular components of the immune recognition process involved in allograft rejection. Graft rejection is initiated by T cells of the recipient recognizing antigens of the foreign graft through clonally- expressed TCRs. The basis of this recognition process is the formation of a trimolecular complex consisting of the TCR, MHC molecule (of the recipient and/or donor type), and a peptide derived from metabolically processed graft antigens. The formation of this complex during immune response to the graft initiates a set of intra- and intercellular reactions that result in destruction of the graft. Hence, elucidation of the nature of the trimolecular complex and the subsequent events involved in the graft rejection will not only broaden our understanding of the rejection process, but may also provide a means to induce graft- specific tolerance. The Specific Aims of this proposal include: 1. Characterization of the TCR repertoire usage by GILs isolated from cardiac allografts performed in rat strain combinations disparate for range of histocompatibility antigens. 2. Establishment of T-cell lines and/or clones from GILs with specific reactivity to graft antigens and examination of their role in mediating cardiac graft rejection following adoptive transfer. 3. Identification of graft antigens that serve as targets for graft- reactive T cells and the analysis of their role in the rejection reaction.