Disease relevance of CD207

• LC-like DCs and freshly isolated epidermal LCs presented nonpeptide antigens of Mycobacterium leprae to T cell clones derived from a leprosy patient in a CD1a-restricted and langerin-dependent manner [1].
• LCs in leprosy lesions coexpress CD1a and langerin, placing LCs in position to efficiently present a subset of antigens to T cells as part of the host response to human infectious disease [1].
• Electron microscopy analysis demonstrated a colocalization of HPV 16 VLPs and langerin, which is expressed only by LC [2].
• A low incidence of Langerin-positive cells was found in tumours and 1/3 of studied carcinomas were even Langerhans cell-free [3].
• Comparison of the expression of Langerin and 175 kD mannose receptor in antigen-presenting cells in normal human skin and basal cell carcinoma [3].

High impact information on CD207

• We have identified a type II Ca2+-dependent lectin displaying mannose-binding specificity, exclusively expressed by Langerhans cells (LC), and named Langerin [4].
• Remarkably, transfection of Langerin cDNA into fibroblasts created a compact network of membrane structures with typical features of BG [4].
• Our data suggest that induction of BG is a consequence of the antigen-capture function of Langerin, allowing routing into these organelles and providing access to a nonclassical antigen-processing pathway [4].
• These immediate precursors expressed CD14, langerin and functional CCR6 [5].
• Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells [1].

Biological context of CD207

• Resident epidermal Langerhans cells (LC) in adult mice express ADPase, major histocompatibility complex (MHC) class II, and CD205 and CD207 molecules, while the first dendritic leukocytes that colonize the fetal and newborn epidermis are only ADPase(+) [6].
• Their LC phenotype was established by the presence CD207 [7].
• A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene [8].
• As anti-langerin antibodies, HPV 16 VLPs were associated with a faster entry kinetics in LC, as reflected by the fact that VLPs were observed near the nuclear membrane of LC within 10 min whereas more than 60 min were needed in DC [2].
• Expression of full-length versions of the four common langerin haplotypes in fibroblasts revealed that all of these forms can mediate endocytosis of neoglycoprotein ligands [9].

Anatomical context of CD207

• Langerin/CD207 sheds light on formation of birbeck granules and their possible function in Langerhans cells [10].
• Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders [11].
• However, it is clear that other C-type lectin receptors such as Langerin on Langerhan cells and mannose receptor on dermal dendritic cells are at least equally important for gp120 binding on epithelial dendritic cells [12].
• The Langerin-positive cells strictly colonized the epidermis and no cells were found in the dermis, where 175 kD mannose receptor-exhibiting cells were present [3].
• The extraepithelial presence of Langerin-positive cells forming contacts with dendrite-like protrusions of 175 kD mannose receptor-exhibiting cells was found in connective tissue surrounding the tumour epithelium and indicates possible cooperation of both elements [3].

Associations of CD207 with chemical compounds

• However, Langerin did bind to surfaces of primary skin fibroblasts and NIH3T3 cells. "Ligand blotting" of fibroblast membrane-enriched fractions with Langerin revealed reproducible binding to 140 and 240 kDa proteins resolved in reduced denaturing gels [13].
• The results are consistent with a role for langerin in internalization of both self and nonself glycoprotein antigens [14].
• In contrast, LC uptake was inhibited only by filipin, and VLP in LC were associated with caveolin, langerin, and CD1a [15].
• Unlike two C-type lectins of leukocytes, L-selectin and Langerin, which also bind to sulphated analogues of sialyl-Le(x), the siglecs do not give detectable binding signals with sulphated analogues that are lacking sialic acid [16].

Regulatory relationships of CD207

• Most importantly, a subset of monocytes cultured with GM-CSF/TGF-beta1 expresses Langerin, as confirmed by electron microscopy analysis [17].
• We conclude that Langerin is coexpressed with CD1a on LCs and LCH [11].

Other interactions of CD207

• They coexpressed LC antigens CD1a and Langerin together with monocyte antigens CD68 and CD14 [18].
• Neither population labeled for Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells [19].
• Namely, both expressed CDla, F-cadherin, and Langerin in the presence of TGF-beta1 and stimulated allogeneic T cells at a similar magnitude [20].
• In contrast to GM-CSF DCs, IL-3 DCs lacked the expression of Birbeck granules (BGs) in spite of their expression of Langerin [20].
• Numerous interleukin-10-positive (IL-10(+)), Langerin(-), and CD68(+) macrophages were found within bone and lymph node lesions [18].

Analytical, diagnostic and therapeutic context of CD207

• As opposed to the uniform absence of donor LC at the time of transplantation, examination of the epidermis from the grafts after 2-4 weeks revealed MHC class II(+) donor cells, which had acquired CD205 and CD207, thus qualifying them as LC [6].
• We have recently combined high resolution two-photon immunofluorescence (using anti MHC-II and Langerin/CD207 antibodies) imaging with microspectroscopy and advanced image-processing/volume-rendering modalities [21].
• Recombinant soluble Langerin did not bind to lymph node or spleen cells, or keratinocytes as assessed via flow cytometry [13].
• In this study, analytical ultracentrifugation and circular dichroism spectroscopy of recombinant soluble fragments of human langerin have been used to show that the extracellular region of this receptor exists as a stable trimer held together by a coiled coil of alpha-helices formed by the neck region [14].
• These results provide evidence for the usefulness of Langerin-directed immuno- and glycohistochemical monitoring of bronchoalveolar lavage fluid in the diagnosis of pulmonary Langerhans cell histiocytosis [22].

References