The identification and characterization of new immunogenic egg components:Implications for evaluation and control of the immunopathogenic T cell response in schistosomiasis

In schistosomiasis, granuloma formation to parasite eggs signals the beginn ing of a chronic and potentially life-threatening disease. Granulomas are s trictly mediated by CD4+ T helper (Th) cells specific for egg antigens; how ever, the number and identity of these T cell-sensitizing molecules are lar gely unknown. We have used monoclonal T cell reagents derived from egg-sens itized individuals 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 b est studied and most abundant egg component is the Sm-p40 antigen. Sm-p40 a nd its peptide 234-246 elicit a strikingly immunodominant Th-1-polarized re sponse in C3H and CBA mice, which are H-2(k) strains characterized by sever e egg-induced immunopathology. Two additional recently described T cell-sen sitizing egg antigens are Schistosoma mansoni phosphoenolpyruvate carboxyki nase (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 eg g granulomas. Importantly, Sm-p40 and Sm-PEPCK have demonstrated immunogeni city in humans. The findings in the murine model introduce the important no tion that egg antigens can vary significantly in immunogenicity according t o the host genetic background. A better knowledge of the principal immunoge nic egg components is necessary to determine whether the immune responses t o certain antigens can serve as indicators or predictors of the form and se verity of clinical disease, and to ascertain whether such responses can be manipulated for the purpose of reducing pathology.