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Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201
A recently cloned major Schistosoma mansoni egg Ag p38
induced and elicited strong Th1-type responsiveness in mice of
H-2k haplotype. Now, we have identified the immunodominant
T cell epitope of p38 and analyzed the dynamics of epitope-specific Th
responsiveness during murine schistosomiasis mansoni. Overlapping
recombinant and synthetic peptides that encompassed the full-length 354
amino acid of p38 were tested for proliferation and cytokine production
in peptide- or p38-sensitized mice. The immunodominant T cell epitope
of p38 that elicited pulmonary granuloma formation was localized within
peptide P4 (amino acids 235–249). The P4-specific cytokine response of
splenocytes that had been sensitized s.c. with p38, P4 or soluble egg
Ags in IFA, or i.p. with 3000 eggs was predominantly as the Th1 type,
with strong IL-2 and IFN-
, but trace amounts of IL-4 and IL-5
secretion. At 6.5 wk of infection, splenocytes and mesenteric lymph
node cells responded to p38/P4 peptides with predominantly Th1-type
responsiveness. This response did not switch to a Th2-type pattern from
8 wk onwards; rather, it underwent down-modulation. Moreover, the
hepatic granuloma lymphocytes at 6.5 wk responded to p38/P4
predominantly with Th1-type cytokine production, indicating that they
participate in early granuloma formation. From 8 wk onwards an immune
deviation to the p38-specific response was observed that was manifested
by rising IgG1, IgE, and IgG2a Ab production as opposed to declining
Th1- and Th2-type cytokine secretion.
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