Technical Information

Technical Information

DEC-205 and Antigen Presentation

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
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

References

  1. Guo, M. et al. (2000) Hum. Immunol. 61:729.
  2. Kato, M. et al. (2000) Int. Immunol. 12:1511.
  3. Inaba, K. et al. (1995) Cell. Immunol. 163:145.
  4. Kronin, V. et al. (2000) Int. Immunol. 12:731.
  5. Henri, S. et al. (2001) J. Immunol. 167:741.
  6. Anjuere, F. et al. (1999) Blood 93:590.
  7. Jiang, W. et al. (1995) Nature 375:151.
  8. Wu, K. et al. (1996) J. Biol. Chem. 271:21323.
  9. Swiggard, W. et al. (1995) Cell. Immunol. 165:302.
  10. Kato, M. et al. (1998) Immunogenetics 47:442.
  11. Mahnke, K. et al. (2000) J. Cell Biol. 151:673.
  12. Hawinger, D. et al. (2001) J. Exp. Med. 194:769.

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