Presentation of a circulating self protein (C5) to MHC class II restricted T cells

Presentation of a soluble self antigen, the fifth component of complement (C5), is discussed with emphasis on the differential ability of presentation by subpopulations of APC (dendritic cells, macrophages, B cells, fibroblasts, B cell lines and bone marrow macrophages). Constitutive presentation of C5 in C5 sufficient mice is a prerequisite for tolerance induction in MHC class II restricted T cells and can be directly demonstrated by the ability of ex-vivo APC from C5 sufficient, but not C5 deficient mice, to activate C5 specific T cells in vitro in the absence of added antigen. C5 presentation and tolerance induction in MHC class II restricted T cells is strictly dependent on an exogenous source of self antigen. C5 biosynthesized, but not secreted by macrophages is ignored by MHC class II restricted cells and induces neither tolerance nor autoimmunity. C5 presentation for tolerance induction depends largely on the efficiency of antigen uptake by APC, a property which varies within different APC subpopulations and with the nature of the antigen.