Schistosoma mansoni: genetic restriction and cytokine profile of the CD4 + T helper cell response to dominant epitope peptide of major egg antigen Sm-p40.
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.
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA.
H J
HJ
Hernandez
C M
CM
Edson
D A
DA
Harn
C J
CJ
Ianelli
M J
MJ
Stadecker
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000469:parasitology; D013997:Time Factors
D000953:Antigens, Protozoan; D016207:Cytokines; D000939:Epitopes; C114086:Sm-p40 antigen