The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen-derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider ‘conventional routes’ of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide–Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross-presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid–CD1 complexes to natural killer T cells and as peptide–Class I MHC complexes to CD8 T cells
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