| 摘要 |
T cells mediate specific immune reactions. They recognize (foreign) protein fragments - peptides - that are bound in the peptide binding groove of MHC molecules. These peptide MHC complexes are generated intracellularly and subsequently transported to the cell surface for recoginition by T cells. A rate limiting step in the MHC restricted presentation of (foreign) peptides derived from extracellular sources is therefore the uptake of such antigens by antigen presenting cells and the delivery to the intracellular compartment(s) where the MHC-peptide complexes are formed. Professional antigen presenting cells like dendritic cells and macrophages take up antigens by macropinocytosis and mannose receptor mediated endocytosis. We have explored the possibility that the mannosylation of otherwise non-mannosylated antigens would lead to enhanced uptake and MHC restricted presentation of (fragments of) such antigens by mannose receptor positive cells. Using mannose receptor positive cultured human dendritic cells as antigen presenting cells we found that the mannosylation of antigenic peptides resulted in a 300 - 10.000 fold enhanced potency to stimulate MHC class II restricted peptide-specific T cell clones compared to non-mannosylated peptides. These results indicate that mannosylation of antigens leads to selective targeting and subsequent superior presentation by dendritic cells, a result which may be applicable in for example vaccine design. |
