ACCESSORY CELLS AND IMMUNE RESPONSES

抗原呈递细胞（APC）将外源抗原加工成肽 与主要组织相容性II类分子结合 复杂和 在质膜上表达，作为克隆的配体， 活化CD 4 + T淋巴细胞。 APC的功能在以下方面至关重要： 免疫反应的启动和调节。 长期目标 这项研究的目的是确定II+类细胞类型， 这一功能在体内。 这将通过良好的- 特征II类转基因小鼠和同种异体骨髓- 表达特定II类分子的重建的SCID小鼠，或 不同细胞类型的单倍型。 这些动物将接种以下疫苗： 可溶性蛋白质抗原可以通过非特异性或非特异性的 机制或受体介导的内吞作用，与颗粒蛋白 需要吞噬作用和细胞内寄生虫。 工作 假设是外来抗原必须竞争 自身蛋白质， II类分子上的肽结合位点;因此， II类+细胞可以是仅针对那些 可通过受体介导的内吞作用浓缩或达到高浓度 浓度作为细胞内生长的结果。 在操作上， 这意味着抗原特异性B细胞是免疫应答所必需的APC。 可溶性蛋白抗原在体内，而巨噬细胞可能是原则 颗粒抗原和专性细胞内寄生虫的APC。 了解哪些II+类细胞类型在体内充当APC 对于活化CD 4 + T细胞的不同形式的抗原将有助于 设计和运送新的合成疫苗。

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.