IMMUNOGENETICS OF TRICHINELLA SPIRALIS

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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.