A cloned major Schistosoma mansoni egg antigen with homologies to small heat shock proteins elicits Th1 responsiveness.
In schistosomiasis mansoni, soluble egg antigens of the worm induce chronic T-cell-mediated granulomatous tissue responses. Since the first preparation of crude soluble egg antigen extract, a dearth of highly purified antigens has hampered the identification of granuloma inducer molecules. Here we report that a cloned 38-kDa egg polypeptide (r38) with homologies to small heat shock proteins is a strong immunogen. The recombinant and the sodium dodecyl sulfate-polyacrylamide gel electrophoresis separated and eluted native 38-kDa (p38) polypeptides, used in microgram amounts and unaided by adjuvant, sensitized mice for a Th1-type immune response, with strong interleukin-2 (IL-2) and gamma interferon secretion but no IL-4 and IL-10 secretion. Extensive cross-reactivity between these two polypeptides was evident. THis pattern was confirmed by reverse transcription-PCR that showed strong IL-2 and gamma interferon message expression but trace amounts of IL-4 message expression in r38-sensitized splenocytes. In mice, the polypeptide induced pulmonary mononuclear granuloma formation around antigen-coupled beads or worm eggs. We propose that the superior immunogenicity of r38 is linked to its relatedness to small heat shock proteins and that the 38-kDa polypeptide may induce the Th1 cytokine responses observed during the early development phase of the egg-induced granuloma.
Cai
Y
Y
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Langley
J G
JG
Smith
D I
DI
Boros
D L
DL
D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D003429:Cross Reactions; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D006099:Granuloma / Q000209:etiology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008171:Lung Diseases / Q000209:etiology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010063:Ovum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000209:etiology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000947:Antigens, Helminth; D016207:Cytokines; D017931:DNA Primers; D018509:DNA, Helminth; D006360:Heat-Shock Proteins; D015801:Helminth Proteins; D012333:RNA, Messenger