Therefore, we expected that both MMR and DEC-205 would recycle through early endosomal compartments and present bound antigens comparably. In fact, both the MMR and DEC-205 mediate adsorptive uptake, and both have cytosolic domains with requisite coated pit localization sequences ( Stahl et al. This 205-kD protein contains 10 external, contiguous, C-type lectin domains and by sequence analysis, is a homologue of the MMR. Previously we have identified an endocytic receptor, termed DEC-205, expressed by dendritic cells (DCs). Incomplete digestion, as occurs with lysosomal enzyme deficiency, leads to vacuolar swelling ( Cohn and Ehrenreich 1969 Ehrenreich and Cohn 1969).Īdsorptive endocytosis receptors, like the macrophage mannose receptor (MMR), FcR, and B cell antigen receptor (BCR), are used in the immune system to facilitate antigen capture and presentation of peptides to T cells ( Bonnerot et al. Digestion must be complete, since amino acids and monosaccharides are then able to diffuse out of the lysosomal system. The ligands for both recycling and nonrecycling families of endocytic receptors are digested in lysosomes down to the level of amino acids. This receptor downregulation can dampen signal transduction. The receptors typically are catabolized in lysosomes, rather than recycled, after uptake of immune complexes and growth factors ( Mellman et al. 1999), have signaling functions in addition to mediating adsorptive uptake of their ligands. 1992a) and certain growth factors ( Wilde et al. Other receptors, e.g., those for immune complexes ( Amigorena et al. By avoiding proteolysis during this recycling, such receptors are ideal for nutrient delivery and scavenging, e.g., cholesterol, iron, and altered glycoproteins. After ligand release in early endosomes, the receptors recycle rapidly to the cell surface. These localize to coated pits, dramatically increasing uptake via coated vesicles. 1983) and asialoglycoprotein receptor ( Ciechanover et al. Many of these receptors function exclusively in endocytosis, such as the prototype low-density lipoprotein receptor (LDLR) ( Brown et al. Several cell surface receptors deliver ligands to the endocytic system for purposes of extensive intracellular digestion within lysosomes. Therefore, the DEC-205 cytosolic domain mediates a new pathway of receptor-mediated endocytosis that entails efficient recycling through late endosomes and a greatly enhanced efficiency of antigen presentation to CD4 + T cells. The mechanism of late endosomal targeting, which occurred in the absence of human IgG, involved two functional regions: a membrane-proximal region with a coated pit sequence for uptake, and a distal region with an EDE triad for the unusual deeper targeting. However, the DEC-205 tail recycled the CD16 through MHC II–positive late endosomal/lysosomal vacuoles and also mediated a 100-fold increase in antigen presentation. The two cytosolic domains each mediated rapid uptake of human immunoglobulin (Ig)G followed by recycling of intact CD16 to the cell surface. To analyze this finding, the cytosolic tails of DEC-205 and MMR were fused to the external domain of the CD16 Fcγ receptor and studied in stable L cell transfectants. We now find in dendritic cells that the DEC-205 multilectin receptor targets late endosomes or lysosomes rich in major histocompatibility complex class II (MHC II) products, whereas the homologous macrophage mannose receptor (MMR), as expected, is found in more peripheral endosomes. Many receptors for endocytosis recycle into and out of cells through early endosomes.

Tails of iron igg