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Murugesan, Gavuthami, Viviana G. Correia, Angelina S. Palma, Wengang Chai, Chunxia Li, Ten Feizi, Eva Martin, Brigitte Laux, Alexandra Franz, Klaus Fuchs, Bernd Weigle, and Paul R. Crocker. "Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression." Glycobiology (2020). Abstract

Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors that plays an important role in osteoclast development and function. It is also expressed by tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-$\beta$. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally-defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-$\beta$ secretion following co-culture of Siglec-15-expressing monocytic cells lines with tumor cells expressing sTn, or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages.

Rudkin, Fiona M., Ingrida Raziunaite, Hillary Workman, Sosthene Essono, Rodrigo Belmonte, Donna M. MacCallum, Elizabeth M. Johnson, Lisete M. Silva, Angelina S. Palma, Ten Feizi, Allan Jensen, Lars P. Erwig, and Neil A. R. Gow. "Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis." Nature communications. 9 (2018): 5288. Abstract

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.

Palma, Angelina S., Benedita Pinheiro, Yan Liu, Yoichi Takeda, Wengang Chai, Yukishige Ito, Maria Joao Romao, Ana Luisa Carvalho, and Ten Feizi. "The Structural Basis of the Recognition of Di-glucosylated N-glycans by the ER Lectin Malectin." Glycobiology. 23 (2013): 1368-1369. Abstract
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Watson, A. A., A. A. Lebedev, B. A. Hall, A. E. Fenton-May, A. A. Vagin, W. Dejnirattisai, J. Felce, J. Mongkolsapaya, A. S. Palma, Y. Liu, T. Feizi, G. R. Screaton, G. N. Murshudov, and C. A. O'Callaghan. "Structural flexibility and ligand-binding characteristics of the macrophage dengue virus receptor CLEC5A." Immunology. 135 (2011): 101. Abstract
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Watson, Aleksandra A., Andrey A. Lebedev, Benjamin A. Hall, Angharad E. Fenton-May, Alexei A. Vagin, Wanwisa Dejnirattisai, James Felce, Juthathip Mongkolsapaya, Angelina S. Palma, Yan Liu, Ten Feizi, Gavin R. Screaton, Garib N. Murshudov, and Christopher A. O'Callaghan. "Structural Flexibility of the Macrophage Dengue Virus Receptor CLEC5A IMPLICATIONS FOR LIGAND BINDING AND SIGNALING." Journal of Biological Chemistry. 286 (2011): 24208-24218. Abstract
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Neu, Ursula, Melissa S. Maginnis, Angelina S. Palma, Luisa J. Stroeh, Christian D. S. Nelson, Ten Feizi, Walter J. Atwood, and Thilo Stehle. "Structure-Function Analysis of the Human JC Polyomavirus Establishes the LSTc Pentasaccharide as a Functional Receptor Motif." Cell Host & Microbe. 8 (2010): 309-319. Abstract
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Neu, Ursula, Stacy-Ann A. Allen, Barbel S. Blaum, Yan Liu, Martin Frank, Angelina S. Palma, Luisa J. Stroh, Ten Feizi, Thomas Peters, Walter J. Atwood, and Thilo Stehle. "A Structure-Guided Mutation in the Major Capsid Protein Retargets BK Polyomavirus." PLoS pathogens. 9 (2013): e1003688. Abstract
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Neu, Ursula, Zaigham Mahmood Khan, Benjamin Schuch, Angelina S. Palma, Yan Liu, Michael Pawlita, Ten Feizi, and Thilo Stehle. "Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands." PLoS pathogens. 9 (2013): e1003714. Abstract
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