Disease relevance of Ly75

• To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs [1].

High impact information on Ly75

• The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing [2].
• Rabbit antibodies that bind DEC-205 are presented to reactive T-cell hybridomas 100-fold more efficiently than rabbit antibodies that do not bind DEC-205 [2].
• We show here that their antigen-presentation function is associated with the high-level expression of DEC-205, an integral membrane protein homologous to the macrophage mannose receptor and related receptors which are able to bind carbohydrates and mediate endocytosis [2].
• Thus DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment [2].
• To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues [3].

Biological context of Ly75

• PU.1(-/-)animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II(+)] CD11c(+) CD8alpha(+) DEC-205(+) [4].
• DEC-205 is rapidly taken up by means of coated pits and vesicles, and is delivered to a multivesicular endosomal compartment that resembles the MHC class II-containing vesicles implicated in antigen presentation [2].
• DEC-205, a 205-kDa protein abundant on mouse dendritic cells and thymic epithelium that is detected by the monoclonal antibody NLDC-145: purification, characterization, and N-terminal amino acid sequence [5].
• After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8alpha and CD205 and the loss of CD4 molecules on their surface [6].
• The targeted MZ DC were quite unique in their phenotype: CD11c(+), CD8alpha(-), CD11b(-), B220(-), and expressing intermediate or low levels of MHC class II and DEC205 [7].

Anatomical context of Ly75

• To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues [8].
• Although CD8alpha and DEC-205 correlate closely among splenic DC, lymph nodes (LN) include a large population of CD8alpha(low) DEC-205(high) DC [9].
• Notably, qualitatively different immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule expressed on CD8alpha+CD4-CD11b- DCs, dermal DCs, and Langerhans cells [10].
• Labeling of IL-12(+) cells for CD11c, CD205, CD8alpha, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c(-) F4/80(+), suggesting that macrophages were an additional source of IL-12 in the skin [11].

Regulatory relationships of Ly75

• GM-CSF-treated cells express both c-Fms and RANK and also low levels of CD11c and DEC205, which are detected on dendritic cells [12].
• Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice [13].

Other interactions of Ly75

• The mature DCs derived from 13 dpc FL Lin(-)c-kit(+) HPCs showed characteristic morphology and function of DCs and expressed high levels of Ia, CD86, and CD40 molecules, low levels of DEC205, E-cadherin, and F4/80 molecules, but barely detectable CD11c antigen [14].
• Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance [8].
• These studies also revealed that DC that matured in response to T cell mitogens display, comparatively to LPS, a distinctive phenotype characterized by high expression of the MHC class II, CD40, and CD205 markers, but only moderate (CD86) to minimal (CD80) expression of CD28/CTLA4 ligands [15].
• With regard to LC maturation, CS but not pimecrolimus inhibited the expression of CD25, CD205, and costimulatory molecules [16].
• A de novo expression of the DC phenotypic markers MIDC8, DEC205, CD11c and relB with up-regulation of surface MHC-II and complete down-regulation of non-specific esterase (NSE) was also observed in peritoneal cells upon GM-CSF treatment [17].

Analytical, diagnostic and therapeutic context of Ly75

• In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination [3].
• In this study we show by confocal microscopy and flow cytometry that cells expressing CD11c, CD205, and MHC class II molecules and containing fluorescently labeled, processed Ag accumulate at the site of intracerebral Ag injection [18].
• Intramuscular injection of FL increased the expression of DEC205 and the size of splenocytes, and immunization with HBc/w or HBc/w-transfected EL-4 cells induced strong anti-HBc antibody responses in mice [19].

References