Macrophage-bound C3 fragments as adhesion molecules modulate presentation of exogenous antigens.
The involvement of complement in the response to T cell dependent antigens is generally accepted, however the mechanism has not been clarified. We compared the T cell response in vitro, using antigen-pulsed macrophages from normal and genetically C3-deficient guinea pigs, and show, that C3-fragments fixed covalently to the surface of the antigen-presenting cells are involved in the triggering of responder T cells. Binding of guinea pig C3-specific mAb to oil-elicited, OVA- and PPD-pulsed macrophages of C3D guinea pigs is reduced compared to normal cells, while the expression of Ia antigens is the same. C3-like peptides can be immunoprecipitated only from the lysate of oil-elicited normal cells. These C3-fragments are fixed to the cell-membrane via ester-bonds, since they are released upon treatment with hydroxylamine. In comparison with normal cells, the antigen-presenting capacity of macrophages derived from C3D animals is strongly impaired in cultures containing 10% normal guinea pig serum. A further impairment is observed in cultures with 10% C3D guinea pig serum. Two of the tested C3-specific mAb inhibited antigen-induced T cell proliferation in a dose-dependent manner. Our data point to the importance of C3, as a bivalent molecule, having the capacity to facilitate the cooperation between the antigen-presenting cell and the responder T lymphocytes.
Erdei
A
A
Department of Immunology, University of L. Eötvös, Göd, Hungary.
Köhler
V
V
Schäfer
H
H
Burger
R
R
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000502:physiology; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001666:Binding Sites, Antibody; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D002458:Cell Fractionation; D002478:Cells, Cultured; D003176:Complement C3 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007399:Interphase; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D009821:Oils / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D011233:Precipitin Tests
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D006898:Hydroxylamines; D008565:Membrane Proteins; D009821:Oils; D010446:Peptide Fragments; D019811:Hydroxylamine