Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones.
The effect of complement fragments C3b and C4b, on the triggering of antigen-specific human T-cell clones by Epstein-Barr virus-transformed human lymphoblastoid B cells (LCL) when these fragments are covalently coupled to the antigen tetanus toxin (TT) is described. TT was chemically cross-linked to purified C3b [(TT-C3b)n], C4b [(TT-C4b)n] or bovine serum albumin [(TT-BSA)n] as a control. T-cell activation was quantified by tritiated thymidine incorporation and 51Cr release. (TT-C3b)n and (TT-C4b)n induced proliferative responses comparable to (TT-BSA)n but at 18-25 and 4-6 lower concentrations, respectively. This enhancing effect required the covalent cross-linking of the complement fragments to the antigen and involved intracellular processing of the latter by LCL. Antigen presentation was similarly enhanced when measuring the cytotoxic activity of a helper T-cell clone against LCL previously pulsed with (TT-C3b)n or (TT-C4b)n compared with (TT-BSA)n. Binding studies, carried out on LCL using TT radiolabelled with 125I before cross-linking, indicated that (TT-C3b)n and (TT-C4b)n gave three- to four-fold more binding than (TT-BSA)n. Addition of antibodies against CR1 and CR2 or proteolytic removal of these complement receptors with trypsin inhibited by about 60% the enhancing effect of TT-bound C3b and C4b in both binding and functional assays. These results indicate that binding of C3b or C4b to antigen enhances antigen-specific proliferative and cytotoxic responses of T cells by targeting opsonized antigen onto complement receptors CR1 and CR2 of LCL. The putative significance of these findings in terms of regulation of immune responses by complement is discussed.
Arvieux
J
J
Departement de Recherches Fondamentales, LBIO/ICH, Unité INSERM, Grenoble, France.
Yssel
H
H
Colomb
M G
MG
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D002999:Clone Cells; D003179:Complement C3b / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology*; D015935:Complement C4b; D006801:Humans; D008213:Lymphocyte Activation; D011951:Receptors, Complement / Q000276:immunology; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D003181:Complement C4; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D013744:Tetanus Toxin; D003179:Complement C3b; D015935:Complement C4b