The molecular basis of granuloma formation in schistosomiasis. II. Analogies of a T cell-derived suppressor effector factor to the T cell receptor.
During Schistosoma mansoni infection, Ts cells regulate granulomatous modulation via antigenically and genetically restricted suppressor inducer and suppressor effector factors. The T suppressor effector factor (TseF) directly suppresses granuloma formation both in vitro and in vivo. In this study, we probe the molecular basis of these TseF properties. Using techniques of heterodimeric chain reduction with DTT and in vitro functional complementation, chimeric molecules were constructed. By analyzing genetic restrictions, antigenic specificities, and phenotypic markers, the contributions of the component chains to 72 kDa TseF reactivity were determined. One chain bore an Ag receptor and imparted antigenic specificity. The other chain bore an IJ determinant, a TCR beta-chain allotypic determinant, a suppressor effector phenotypic determinant, and imparted functional genetic restriction. Functional activity required covalent, probably sulfhydryl mediated, linkage as succinylation prevented the separated component chains from reconstituting functional activity. Additional studies demonstrated that anti-serum directed against either the T cell receptor or the T3 epsilon-chain could abrogate functional activity. However, TseF bore no T3 epsilon-chain phenotypic marker per se suggesting that TseF effects T lymphocytes via transmembrane signal transduction. These studies suggest that a regulatory network is operative in granuloma modulation. This regulatory network is mediated by a soluble TseF that bears significant structural homologies to the classic TCR.
Perrin
P J
PJ
Allergy and Immunology Section, University of Pennsylvania School of Medicine, Philadelphia 19104.
Prystowsky
M B
MB
Phillips
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001667:Binding, Competitive; D000939:Epitopes; D006099:Granuloma / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D008970:Molecular Weight; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D013387:Succinic Anhydrides; D013491:Suppressor Factors, Immunologic / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C043911:I-J-antigen; D011948:Receptors, Antigen, T-Cell; D013387:Succinic Anhydrides; D013491:Suppressor Factors, Immunologic; C031801:succinic anhydride