Complement C3b fragment covalently linked to tetanus toxin increases lysosomal sodium dodecyl sulfate-stable HLA-DR dimer production.

Processing and presentation of covalently linked C3b-tetanus toxin (TT) complexes, as compared to unlinked C3b + TT, lead to increased T cell proliferation. The aim of this study was to analyze the effect of coupling C3b to TT on the efficiency of TT peptide loading on HLA-DR1 molecules. In the Epstein-Barr virus-transformed B cell line HOM 2, we detected a significant increase of sodium dodecyl sulfate (SDS)-stable major histocompatibility complex (MHC) class II molecules after exposure to C3b-TT as compared to unlinked C3b and TT. The ratio of compact form/unbound form (C/U ratio) obtained with C3b-TT as antigen (Ag) is about twice that obtained with uncomplexed TT + C3b as Ag. Similar results were obtained using HLA-DR1-transfected fibroblasts that do not express C3b complement receptors, indicating that the SDS-stable HLA-DR1 increase did not result simply from C3b opsonization but rather from a direct effect of C3b-TT linkage on peptide generation. Exposure of HOM 2 cells to C3b-TT resulted in an increase in concentration of SDS-stable HLA-DR molecules in lysosomes but not in endosomes. Thus, C3b attachment to Ag induces a redistribution of peptide/MHC complex which results in a higher efficiency of Ag presentation by MHC class II molecules.

Heat shock increases antigenic peptide generation but decreases antigen presentation.

The heat shock response is a universal and highly conserved cellular response to stress. We describe here the effect of elevated temperature on the capacity of B cells to present antigen. Heat shock markedly affects the ability of these cells to process and present tetanus toxin to class II-restricted T cell clones. Inhibition of antigen presentation is due neither to a modification of antigen capture nor to a variation of major histocompatibility complex (MHC) class II molecule synthesis and cell surface expression. Stressed and nonstressed B cells are able to present peptides loaded at the cell surface with the same efficiency. Nevertheless, heat shock leads to an increase of antigen peptide generation in subcellular compartments; an enhancement of cathepsin B activity is also observed. These data suggest that such a stress induces a failure in the intracellular peptide loading onto MHC class II molecules.