Functional recognition of in vivo processed self antigen

C5, the fifth component of complement, is a circulating self protein which induces complete tolerance in MHC class II restricted, CD4+ T cells due to the presentation of C5 taken up from plasma. Functional recognition of in vivo processed C5 was monitored by activation of C5 specific T cell hybrids cultured with antigen presenting cells (APC) from C5 expressing mice. Dendritic cells isolated from various tissues (spleen, thymus, skin) proved to be the most efficient APC, since 10- to 50-fold more macrophages and at least 100- to 500-fold more B cells were needed to achieve similar T cell activation. Stimulatory C5 peptide--class II complexes generated in vivo were retained on the surface of dendritic cells but not on macrophages and B cells upon prolonged culture. Dendritic cells but not macrophages from thymus presented in vivo processed C5. Taken together these findings emphasize the crucial role dendritic cells play for recognition of soluble self proteins by MHC class II restricted T cells.