Analysis of egg antigens inducing hepatic lesions in schistosome infection.
In schistosomiasis, granuloma formation to parasite eggs signals the beginning of a chronic and potentially life-threatening disease. Granulomas are strictly mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the number and identity of these T cell-sensitizing molecules are largely unknown. We have used monoclonal T cell reagents as probes to track down, isolate and positively identify several egg antigens; this approach implicitly assures that the molecules of interest are T cell immunogens and, hence, potentially pathogenic. The best-studied egg component is the Sm-p40 antigen. Sm-p40 elicits a strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are characterized by severe egg-induced immunopathology. Two additional described T cell-sensitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx-1). In contrast to Sm-p40, both of these molecules induce a more balanced Th-1/Th-2 response, and are relatively stronger antigens in C57BL/6 mice, which develop smaller egg granulomas. Other components, including moieties with molecular weights of 25 kDa (Sm-p25), 150/166 kDa (Sm-p155/166), and 29 kDa (Sm-GST29), are also found to stimulate specific T cells. These findings in the murine model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background. A better knowledge of the principal immunogenic egg components is necessary to ascertain whether such responses can be manipulated for the purpose of reducing pathology.
Asahi
Hiroko
H
Department of Parasitology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. asahih@nih.go.jp
Stadecker
Miguel J
MJ
D000818:Animals; D000909:Antibodies, Helminth; D000947:Antigens, Helminth / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000090266:Chromobox Protein Homolog 5; D005260:Female; D006801:Humans; D008099:Liver / Q000469:parasitology* / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D010063:Ovum / Q000737:chemistry*; D012552:Schistosomiasis / Q000473:pathology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; C000715594:CBX5 protein, human; D000090266:Chromobox Protein Homolog 5