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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.