DEC-205 is a type I cell surface protein expressed primarily by dendritic cells (DC). It is found on interdigitating DC in T cell areas of lymphoid tissues, bone marrow-derived DC, Langerhan’s cells, and at low levels on macrophages and T cells.1-3 It is significantly up-regulated during the maturation of DC.1-3 Expression of DEC-205 is positively correlated with that of CD8a, both being found at high levels on lymphoid DC and at low levels on myeloid DC.4-6 DEC-205 is also expressed at moderate levels by B cells and is up-regulated during the pre-B cell to B cell transition.3 Tissue distribution of DEC-205 is comparable between human and mouse.1 DEC-205 belongs to a family of C-type multilectins which also includes the macrophage mannose receptor (MMR), the phospholipase A2 receptor (PLA2R),7 and a fourth unnamed receptor.8 Structurally, this family is characterized by a cysteine rich N-terminal domain followed by a fibronectin type II domain and multiple carbohydrate recognition domains (CRDs).7 DEC-205 has ten CRDs whereas other family members have eight.7 The single transmembrane domain is followed by a short cytoplasmic tail (see Figure 1).7
|Figure. 1. After binding DEC-205, antigens are internalized, processed, and presented on the DC surface in a complex with major histocompatibility complex (MHC) II (left panel). DEC-205 is a C-type multilectin with a cysteine rich N-terminal domain followed by a fibronectin II domain and 10 carbohydrate recognition domains (CRDs). It has a single transmembrane domain with a short cytoplasmic tail (right panel).|
The 205 kDa molecular weight includes approximately 7 kDa of carbohydrates found in eight glycosylation branching variants, all of which are N-linked.9 The appearance of multiple bands on SDS-PAGE corresponds to degradation fragments and suggests the presence of protease resistant domains separated by more sensitive linkers.9
Amino acid sequence comparison between human and mouse DEC-205 indicates a 77% identity with conservation of all cysteine locations and putative N-linked glycosylation sites.10 Amino acid sequences are less well conserved between DEC-205 and MMR (29%) and PLA2R (35%)7 not withstanding a strong structural similarity. Both human and mouse DEC-205 are encoded by single copy genes. The message is found in two splice variants, but the protein is encoded from a single cDNA of 5166 bp.10
The ligand binding specificity of DEC-205 has not been described. There is some evidence that DEC-205 recognizes protein modifications other than the glycosylations recognized by MMR.2 It is apparent that mouse DC have mannosylated antigen uptake mechanisms besides MMR.
Both DEC-205 and MMR are important for uptake of extracellular proteins (see Figure 1). Anti-DEC-205 antibodies are internalized via coated vesicles and are delivered to an endosomal compartment active in antigen processing and rich in MHC II and LAMP-1.7,11 In contrast, MMR mediated uptake is not an effective pathway for antigen presentation. Very little MMR can be detected in late endosomes or lysosomes.11
After binding to DEC-205, proteins are internalized, processed, and presented in a complex with MHC II.7 Cognate T cells are stimulated to proliferate, but there is no induction of Th1 or Th2 polarization.4,12
The most detailed structural studies of DEC-205 have focused on its cytoplasmic tail. The tails of both DEC-205 and MMR mediate ligand uptake, intracellular discharge, and receptor recycling to the cell surface.11 The deep endosomal targeting of ligands taken up via DEC-205 is mediated by amino acids 18-31 within its C-terminal tail, a region not found within MMR.11 If the 18-31 amino acid region is deleted, mutant receptors can still internalize with bound ligand and recycle to the cell surface but no longer participate in efficient antigen presentation.11
- Guo, M. et al. (2000) Hum. Immunol. 61:729.
- Kato, M. et al. (2000) Int. Immunol. 12:1511.
- Inaba, K. et al. (1995) Cell. Immunol. 163:145.
- Kronin, V. et al. (2000) Int. Immunol. 12:731.
- Henri, S. et al. (2001) J. Immunol. 167:741.
- Anjuere, F. et al. (1999) Blood 93:590.
- Jiang, W. et al. (1995) Nature 375:151.
- Wu, K. et al. (1996) J. Biol. Chem. 271:21323.
- Swiggard, W. et al. (1995) Cell. Immunol. 165:302.
- Kato, M. et al. (1998) Immunogenetics 47:442.
- Mahnke, K. et al. (2000) J. Cell Biol. 151:673.
- Hawinger, D. et al. (2001) J. Exp. Med. 194:769.