Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera.
Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide range of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D) alpha epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
Nilsson
B
B
Department of Clinical Immunology, University Hospital, Uppsala, Sweden.
Ekdahl
K N
KN
Svensson
K E
KE
Bjelle
A
A
Nilsson
U R
UR
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D011863:Radioimmunoassay; D012217:Rheumatoid Factor / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D003176:Complement C3; D000939:Epitopes; D012217:Rheumatoid Factor