Schistosoma mansoni: genetic restriction and cytokine profile of the CD4 + T helper cell response to dominant epitope peptide of major egg antigen Sm-p40.

Abstract

Granuloma formation in schistosomiasis is mediated by MHC class II-restricted CD4 + T helper lymphocytes sensitized to egg antigens. We previously reported that C3H mice, which develop large granulomas, display strong CD4 + T helper cell responses to the major egg antigen Sm-p40. Moreover, all members of a panel of egg antigen-specific T cell hybridomas responded to the Sm-p40 antigen. Given the significance of the Sm-p40 molecule in the C3H T cell repertoire against schistosomal egg antigens, the current work was undertaken to map its immunogenic epitopes, using a library of 15 synthetic overlapping 30-mer peptides. The dominant epitope recognized by polyclonal CD4 + Th cells was located in peptide 10 (amino acids 229-258); subdominant epitopes were detected in peptides 8 (amino acids 179-208) and 12 (amino acids 279-308). The anti-Sm-p40 T cell hybridomas variously responded to any one of the same three stimulatory peptides. Furthermore, studies with various mouse strains demonstrated that a strong anti-Sm-p40 response was restricted by H-2(k). Interestingly, the cells responding to peptide 10 and to the Sm-p40 antigen only secreted IL-2 and IFN-gamma, but not IL-4 and IL-10, indicating that they are entirely of the Th-1-type, a subset with demonstrated capacity to mediate egg granuloma formation. The identification of dominant epitopes within key egg antigens offers opportunities for desensitization of the CD4 + Th cells that mediate pathology in schistosomia sis.

• Authors: H J Hernandez, C M Edson, D A Harn, C J Ianelli, M J Stadecker
• Journal: Experimental parasitology (Exp Parasitol) Vol. 90 Issue 1 Pg. 122-30 (Sep 1998) ISSN: 0014-4894 [Print] United States
• PMID: 9709038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• Antigens, Protozoan
• Cytokines
• Epitopes
• Sm-p40 antigen

Topics

• Animals
• Antigens, Protozoan (genetics, immunology)
• Cytokines (biosynthesis)
• Epitopes (immunology)
• Female
• Hybridomas
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Inbred DBA
• Schistosoma mansoni (immunology)
• Schistosomiasis mansoni (immunology)
• Species Specificity
• T-Lymphocytes, Helper-Inducer (immunology, parasitology)
• Time Factors