The larval stage of the intestinal nematode, Trichinella spiralis, secretes and displays on its cuticle a number of antigenically cross-reactive glycoproteins. These so-called TSL-1 antigens induce a powerful antibody response in parasitized animals. In rats, anti-TSL-1 antibodies mediate a protective immunity that expels invading larvae from the intestine. The vast majority of anti-TSL-1 antibodies are specific for glycans. Although the biological functions of TSL-1 antigens are not known, the powerful effect of glycan-specific antibodies on the intestinal survival of T. spiralis suggests that they play an important role in parasite establishment. Little is known about the structures of the glycans present on the TSL-1 glycoproteins. Recent studies have suggested, however, that the antigens contain very unusual glycans (Wisnewski, N., McNeil, M., Grieve, R.B. and Wassom, D.L., Mol. Biochem. Parasitol., 61, 25-36, 1993). Sugar and linkage analysis of the combined secreted products unexpectedly showed that a major terminal sugar is tyvelose (3,6-dideoxy-D-arabino-hexose; Tyv) which has previously been found only in certain gram-negative bacterial lipopolysaccharides. In this paper, we report the first rigorous structural study of oligosaccharides released from TSL-1 antigens by peptide N-glycosidase F digestion. Using strategies based on fast atom bombardment mass spectrometry (FAB-MS), we have discovered a novel family of tri- and tetra-antennary N-glycans whose antennae are comprised of the tyvelose-capped structure: Tyv1,3GalNAc beta 1,4(Fuc alpha 1,3)GlcNAc beta 1-. Thus a major population of TSL-1 glycans contains clusters of hydrophobic terminal structures which are likely to be highly immunogenic.
SllmmaryVitamin A-deficient (A-) mice make strikingly poor IgG responses when they are immunized with purified protein antigens. Previously, we showed that A-T cells overproduce interferon 3' (IFN-3"), which then could inhibit interlenkin 4 (ID4)-stimalated B cell IgG responses. To determine if the altered IFN-3' regulation pattern and its immunological consequences would extend to a natural infection, we studied mice infected with the parasitic hdminth Trichinella spiralis. The course of the infection was similar in A-and A-sufficient (A +) mice. These mice did not differ with respect to newborn larvae/female/hour produced in the intestine, or muscle larvae burden 5 wk postinfection. They also did not differ in the intestinal worm expulsion rate until day 15, when A-mice still harbored parasites, whereas A § mice had cleared intestinal worms. Vitamin A deficiency reduced both the frequency of B lymphocytes secreting IgG1 antibodies to parasite antigens, and the bone marrow eosinophilia associated with hdminth infection. The cytokine secretion patterns in infected mice were consistent with these observations and with previous studies. Mesenteric lymph node cells from infected A-mice secreted siguificantly more IFN-3", and significantly less IL-2, IL-4, and IL-5 than infected A § controls. A-splenocytes secreted significantly more IFN-3', and equivalent amounts of IL-2, Ih-4, and IL-5 compared with A + controls. Interestingly, CD4-CDS-cells secreted the majority of the Ib4 produced in the spleen. The II.,2, Ib4, and Ib5 steady-state transcript levels correlated with secreted protein levels, but IFN-3' transcripts did not. Although they secreted more protein, A-cells contained fewer IFN-3" transcripts than A + cells. These results suggest two vitamin A-mediated regulation steps in IFN-3" gene expression: positive regulation of IFN-3' transcript levels, and negative regulation posttranscriptionally. The essentially unaltered outcome of T. spiralis infection in vitamin A-deficient mice probably reflects a balance between cellular and humoral responses. The IFN-3' overproduction might have a positive effect on the gut inflammatory response, but the decreased eosinophilia, cytokine production in mesenteric lymph node, and IgGl-secreting cell frequency might have a negative effect on T, spiralis immunity.
Results indicated the presence of HDMs and HDM allergens in the specific microenvironment of dogs in homes. Factors associated with high levels of exposure were identified, which may be associated with increased risk for sensitization and development of atopic diseases.
Two panels of H-2 recombinant strains of mice were used in an attempt to map the H-2-linked genes which control resistance to infection with Trichuris muris. Response phenotypes could be related to the presence of 'resistance' (q,b) or 'susceptibility' (k,d) alleles at I-A. The influence of these genes was modulated by other alleles, particularly q or d alleles, at the D end of the H-2. Absence of I-E molecules correlated with resistance to infection in some but not all strains studied. Thus the (B10.BR x B10.G) F1 strain which expressed I-Ek gene products was resistant to infection. A study of the time-course of infection in strains of mice expressing q alleles throughout the H-2 on 4 different genetic backgrounds (NIH, SWR, DBA and B10) revealed that most strains were resistant to infection. However, the DBA/1 strain exhibited differential responsiveness, 4 out of 6 individuals harbouring mature adult parasites on day 35 post-infection.
In order to characterize immunodominant components of T. spiralis a workshop was organized. In this the reactivity of monoclonal and polyclonal antibodies, provided by different research groups, towards total extracts from adult, new born larvae and muscle larvae as well as to excretory/secretory components of muscle larvae were tested by ELISA, Western blot and immunoprecipitation assays. As a result of this workshop T. spiralis ML antigens have been classified into eight groups (TSL-1-TSL-8) according to their recognition by monoclonal and polyclonal antibodies. Among them, TSL-1 antigens have been the most extensively characterized both biochemically and immunologically. These antigens are stage specific, originate in the muscle stichosome and are abundant in both E/S and on the larval cuticular surface. The TSL-1 antigens share an immunodominant carbohydrate epitope (tyvelose), which is unique for Trichinella and is not associated with phosphorylcholine. The data collected in this workshop has allowed both the unification of the nomenclature for T. spiralis antigens and their biochemical characterization. It also has provided a platform for further studies on the characterization of other T. spiralis antigens and indeed for other Trichinella species.
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