A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells.

Abstract

Murine cells of the B lymphoblastoid line A20 and concanavalin A-elicited peritoneal macrophages are shown to activate and fix C3 fragments covalently when incubated in fresh, autologous serum under conditions allowing the initiation of the alternative complement pathway. For the detection of cell-bound C3, cytofluorimetry was performed using FITC-labeled F(ab')2 fragments of anti-mouse C3. Cell-bound C3 fragments are not internalized or shed by the cells under culture conditions for at least two hours. When the antigen-presenting capacity of serum-treated cells was tested using various antigens and experimental systems, augmentation of the proliferation of antigen-specific T cells was found. This enhancing effect was particularly pronounced at suboptimal antigen doses. The elevation of T cell proliferation induced by C3-opsonized antigen-presenting cells (APC) could be abrogated by F(ab')2 fragments of goat anti-mouse C3, suggesting the involvement of C3 receptors expressed by T cells in the process. Using the 7G6 mAb recognizing murine CR1/CR2, the presence of these complement receptors on activated T cells is demonstrated by cytofluorimetry and immunoprecipitation, as well. These results point to the role of C3 bound to acceptor sites on APC in the facilitation of antigen presentation, providing a further link between innate and adaptive immunity.

Complement Component 3 Is Required for Optimal Expansion of CD8 T Cells During a Systemic Viral Infection

“…Although the underlying mechanisms are still unclear, it has been reported that C3 deposition on APCs augments T cell proliferation (40,45). Taken together, these reports suggest that lack of C3 activity can also affect the efficiency of Ag presentation, thereby limiting the expansion of LCMV-specific CD8 T cells in vivo.…”

“…CR1/CR2 signaling in B cells regulates activation threshold, Ag uptake, processing and presentation, isotype switching, and generation of memory B cells (9). Moreover, expression of CR1/CR2 on T cells has been reported, and may promote binding between the APC and T cells via C3 (16,40,45). Therefore, C3 can regulate T cell responses by interacting directly with T cells or indirectly via APCs.…”

Inhibition of Complement Alternative Pathway Suppresses Experimental Autoimmune Anterior Uveitis by Modulating T Cell Responses

“…It has become apparent that the stimulation and activation of T cells depend not only on the presentation of the peptide-MHC complex by APCs in lymph nodes or secondary lymphoid organs but also include various other factors (46). Studies in the literature suggest that the complement plays an important role in antigen presentation by APCs as well as antigen-specific T cell responses (20,21,(47)(48)(49).…”

Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen‐induced arthritis

“…An intriguing candidate gene for Ciaa3 is the complement 3 gene (C3) which maps at the extreme centromeric end of chromosome 9 (62). Activation products of C3 enhance both antigen-specific T cell activation (63) and subsequent autoantibody formation (64). C3b-antigen complexes promote macrophage processing of antigen and presentation of antigenic peptides to T cells (65).…”