ROLE OF ACCESSORY CELLS IN IMMUNE RESPONSES

抗原提呈细胞(APC)将外来抗原加工成多肽 它们被主要组织相容性的II类分子结合 复合体，并在质膜上作为克隆配体表达 CD4+T淋巴细胞的活化。APC的功能在 免疫反应的启动和调节。远距离目标 这项研究的目的是确定执行任务的II+类细胞类型 这一功能在体内发挥作用。这将通过使用油井- 特征为II类转基因小鼠和异基因骨髓- 重组SCID小鼠，表达特定的II类分子或 不同细胞类型的单倍型。这些动物将被接种疫苗 可通过以下两种方式内化的可溶性蛋白质抗原 受体介导的内吞作用机制，与颗粒蛋白 需要吞噬和细胞内寄生虫。在工作中 假说是外来抗原必须与自身蛋白竞争 II类分子上的肽结合部位；因此， 类II+细胞只有对其所表达的抗原才是有效的APC 可通过受体介导的内吞作用进行浓缩或达到高 细胞内生长所产生的浓度。在操作上，这是 意味着抗原特异性B细胞是APC所必需的 体内的可溶性蛋白抗原，而巨噬细胞可能是主要的 颗粒抗原和专性细胞内寄生虫的APC。 了解哪些II+类细胞类型在体内发挥APC的作用 对于活化的CD4+T细胞来说，对不同形式的抗原会有所帮助 在设计和交付新的合成疫苗方面。

Antigen-presenting cells (APCs) process foreign antigens into peptides that are bound by class II molecules of the Major Histocompatibility Complex and expressed on the plasma membrane as the ligand for clonal activation of CD4+ T lymphocytes. The function of APCs is critical in the initiation and regulation of immune responses. The long range goal of this research is to identify the class II+ cell types which perform this function in vivo. This will be accomplished using well- characterized class II transgenic mice and allogeneic bone marrow- reconstituted SCID mice that express a particular class II molecule or haplotype on different cell types. These animals will be immunized with soluble protein antigens that can be internalized via either non-specific mechanisms or receptor-mediated endocytosis, with particulate proteins requiring phagocytosis and with intracellular parasites. The working hypothesis is that foreign antigens must compete with self proteins for the peptide binding site on a class II molecule; and, therefore, a class II+ cell can be an effective APC only for those antigens that it can concentrate by receptor-mediated endocytosis or that reach high concentrations as a result of intracellular growth. Operationally this would mean that antigen-specific B cells are the requisite APCs for soluble protein antigens in vivo, while macrophages may be the principle APCs for particulate antigens and obligate intracellular parasites. A knowledge of which class II+ cell types function as APCs in vivo for the activation CD4+ T cells to different forms of antigen will aid in the design and delivery of new synthetic vaccines.