Immunodominance of the Sm-p40 antigen contributes to the development of severe schistosomiasis mansoni (99.5)

Abstract

Abstract In murine schistosomiasis, H-2k CBA and C3H mice develop severe CD4 T cell(CD4) mediated liver pathology(LP) and a high Th1/17 response very focused on a single epitope of the parasite egg antigen Sm-p40(p234-246). Low pathology C57BL/6 mice do not recognize this antigen. A possible reason for this result is that p234-246 exacerbated dominance(ED) polarizes the anti-egg response causing severe LP. To test this hypothesis we: a)analyze the LP of SJL mice whose H-2 haplotype also exhibit ED of a single Sm-p40 epitope and b) analyze the LP of CBA mice whose p234-246 ED was neutralized by an epitope cocktail. Methodology:H-2s Sm-p40 restriction pattern was determined with the rankpep software. SJL LP was documented by comparative liver morphometric analysis(LMA) of infected CBA, C57BL/6 and SJL mice euthanized 7 weeks-post-infection(wpi). The effect of p234-246 ED neutralization was studied by LMA of 3 groups of infected CBA mice euthanized at 7wpi. The 1st group was treated with an emulsion of adjuvant and 4 synthetic epitopes designed to compete for I-Ak with an affinity equal or higher than p234-246, the 2nd was treated with adjuvant alone and the 3rd was not treated. Results:LMA shows that SJL mice develop as severe a LP as CBA mice and that p234-246 ED neutralization prevents development of severe LP. Conclusion:These results show that ED may be pathogenic in CD4 mediated diseases and that its neutralization may be an effective therapeutic strategy that deserves exploration.