A novel 62-kilodalton egg antigen from Schistosoma mansoni induces a potent CD4(+) T helper cell response in the C57BL/6 mouse

In infection with Schistosoma mansoni, hepatic granuloma formation is media ted by CD4(+) T helper (Th) cells sensitized to schistosomal egg antigens, There is considerable variation among infected individuals with respect to both severity of disease and the T-cell response to egg antigens, In the BL /6 mouse, the egg granulomas are relatively small and the relevant sensitiz ing egg antigens are largely unknown. We investigated the CD4(+) Th cell re sponse of infected BL/6 mice to egg antigens fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and found a prominent lymphopro liferative response to be directed against a 62-kDa component. With the aid of a specific T-cell hybridoma, 4E6, the 62-kDa antigen was isolated; foll owing partial digestion with endoproteinase Glu-C, an internal amino acid s equence was found to be identical with one present in the enzyme phosphoeno lpyruvate carboxykinase (PEPCK) of the organisms Caenorhabditis elegans and Treponema pallidum and to differ by one residue from PEPCK of various othe r species. In CD4(+) Th cells from 7.5-8.5-week-infected BL/6 mice, the pur ified 62-kDa molecule elicited a potent proliferative response which, based on cytokine analysis, was of a mixed Th-1 and Th-2 type. Our results revea l a novel egg antigen of particular prominence in the BL/6 mouse and sugges t that the immune response in schistosomiasis is a product of sensitization to egg antigens that may vary considerably in immunogenicity from strain t o strain.