IMMUNOGENETICS OF TRICHINELLA SPIRALIS

表达H-2编码的I-E分子的小鼠 对T.螺旋感染的小鼠比没有螺旋感染的小鼠多。 两 另外的H-2基因和4号染色体上的基因也是已知的 来影响抗旋毛虫反应 实验 建议比较表型表达的细胞和 由每个基因调节的体液抗寄生虫反应 鉴定 用于细胞和分子机制的研究 这是I-E表达与 感染的易感性，表达I-E的转基因小鼠将 通过将E α基因插入I-E阴性的 具有E β功能基因的小鼠。 H-2同源 小鼠品系和从交配中选择的后代 将研究这些菌株以确定某些I-E等位基因是否 与感染易感性相关而另一些则不相关。 在 此外，Fv-1同源小鼠品系和杂交后代 将研究它们之间的关系，以更精确地绘制基因图， 影响抗旋毛虫反应的4号染色体， 并确定控制I-J表达的基因 与控制对T.旋毛虫 感染 最近开发的寄生虫计数方法- 将使用特异性抗体分泌细胞，沿着 克隆群体，T.螺旋体特异性T细胞，以识别和 表征I-J阳性旋毛虫特异性抑制性T细胞， 并确定具有调节功能的自身反应性T细胞 在T的过程中出现。螺旋体感染 功能 来自寄生虫不同发育阶段的抗原将被 用敏感和抗性小鼠的血清表征 菌株从可溶性蠕虫提取物中沉淀抗原。 单克隆抗体将用于亲和纯化相关的 从这些制剂中提取抗原。 调节免疫 对纯化至同质的保护性抗原的反应， 在小鼠中比较敏感和耐药菌株。 长 这个项目的目标是确定免疫调节 在宿主的敏感和抗性菌株上有所不同。

Mice which express H-2 encoded I-E molecules are more susceptible to T. spiralis infection than mice which do not. Two additional H-2 genes and a gene on chromosome 4 are also known to influence the anti-Trichinella response. Experiments are proposed to compare the phenotypically expressed cellular and humoral anti-parasite responses regulated by each of the genes identified. For studies on the cellular and molecular mechanisms which underly the association between I-E expression and susceptibility to infection, transgenic mice which express I-E will be constructed by inserting the E alpha gene into I-E-negative mice which possess a functional gene at E beta. H-2 congenic strains of mice and selected offspring from matings between these strains will be studied to determine if certain I-E alleles are associated with susceptibility to infection while others are not. In addition, Fv-1 congenic strains of mice and offspring from crosses between them will be studied to more precisely map the gene on chromosome 4 which influences the anti-Trichinella responses, and to determine if the gene controlling I-J expression cosegregates with the gene controlling susceptibility to T. spiralis infection. A recently developed assay to enumerate parasite- specific antibody secreting cells will be used, along with populations of cloned, T. spiralis-specific T cells, to identify and characterize I-J positive, Trichinella-specific suppressor T cells, and to determine if autoreactive T cells with regulatory functions arise during the course of a T. spiralis infection. Functional antigens from different development stages of the parasite will be characterized using serum from susceptible and resistant mouse strains to precipitate antigens from soluble worm extracts. Monoclonal antibodies will be used to affinity purify relevant antigens from these preparations. Regulation of the immune response to protective antigens, purified to homogeneity, will be compared in susceptible and resistant strains in mice. The long range goal of this project is to determine how immune regulation differs in susceptible and resistant strains of hosts.