Prediction of Epitopes in Closely Related Proteins Using a New Algorithm

Davydov, Iakov I.; Fidalgo, Sara; Khaustova, S. A.; Lelyanova, V. G.; Grebenyuk, E. S.; Ushkaryov, Yuri A.; Tonevitsky, Alexander G.

doi:10.1007/s10517-010-0838-y

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…Mouse monoclonal antibody against FLRT3 was obtained from Santa Cruz Biotechnology (Heidelberg, Germany). The polyclonal rabbit anti-peptide antibody (PAL1) against LPHN1 was described previously ( Davydov et al, 2009 ). LTX was purified as previously described ( Ashton et al, 2000 ).…”

Section: Methodsmentioning

confidence: 99%

The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

et al. 2017

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Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)-dependent manner. Tim-3 participates in galectin-9 secretion and is also released in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic lymphoid cells including natural killer (NK) cells. Soluble Tim-3 prevents secretion of interleukin-2 (IL-2) required for the activation of cytotoxic lymphoid cells. These results were validated in ex vivo experiments using primary samples from AML patients. This pathway provides reliable targets for both highly specific diagnosis and immune therapy of AML.

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Section: Methodsmentioning

confidence: 99%

The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

et al. 2017

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“…The following antibodies were used in this work: Rabbit anti-NF-H (Neuromics, RA22116); mouse anti-MAP-2 (Neuromics, MO22116); mouse monoclonal anti-V5 (clone SV5-Pk1, AbD Serotec/Bio-Rad, MCA1360); rabbit anti-V5 (Thermo Fisher Scientific, PA1-29324; RRID: AB_1961277 ); mouse monoclonal anti-myc (clone 9E10, Millipore, 05–419; RRID: AB_309725 ); chicken anti-myc (Millipore, AB3252; RRID: AB_2235702 ); mouse anti-FLAG M2 (Sigma-Aldrich, F3165; RRID: AB_259529 ); anti-FLAG M2 affinity gel (Sigma-Aldrich, A2220); mouse anti-actinin (Sigma-Aldrich, A7811); rabbit polyclonal anti-LPHN1-peptide (PAL1, ( Davydov et al, 2009 ); rabbit polyclonal anti-LPHN1 NTF (RL1) ( Davletov et al, 1998 ); mouse anti-Lasso/TEN2 C-terminus (TN2C, dmAb) ( Silva et al, 2011 ); sheep anti-TEN2 N-terminus (TN2N, R and D systems, AF4578; RRID: AB_10719438 ); mouse anti-synapsin (Santa-Cruz Biotechnology, sc-376623; RRID: AB_11150313 ); rabbit anti-PSD-95 (Millipore, AB9708; RRID: AB_11212529 ); rabbit anti-Tau (Synaptic Systems, 314 002; RRID: AB_993042 ); rabbit anti-GFP (Thermo Fisher Scientific, A-11122; RRID: AB_221569 ).…”

Section: Methodsmentioning

confidence: 99%

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones

Vysokov

Silva

Lelianova

et al. 2018

eLife

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A presynaptic adhesion G-protein-coupled receptor, latrophilin-1, and a postsynaptic transmembrane protein, Lasso/teneurin-2, are implicated in trans-synaptic interaction that contributes to synapse formation. Surprisingly, during neuronal development, a substantial proportion of Lasso is released into the intercellular space by regulated proteolysis, potentially precluding its function in synaptogenesis. We found that released Lasso binds to cell-surface latrophilin-1 on axonal growth cones. Using microfluidic devices to create stable gradients of soluble Lasso, we show that it induces axonal attraction, without increasing neurite outgrowth. Using latrophilin-1 knockout in mice, we demonstrate that latrophilin-1 is required for this effect. After binding latrophilin-1, Lasso causes downstream signaling, which leads to an increase in cytosolic calcium and enhanced exocytosis, processes that are known to mediate growth cone steering. These findings reveal a novel mechanism of axonal pathfinding, whereby latrophilin-1 and Lasso mediate both short-range interaction that supports synaptogenesis, and long-range signaling that induces axonal attraction.

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“…ELISA-based assay kits for the detection of IL-6, was from R&D Systems (Abingdon, UK). The polyclonal rabbit anti-peptide antibody PAL1 against LPHN1 and polyclonal mouse antibody dmAb against Lasso/teneurin-2 were previously described [20, 21]. Human SCF [22] and anti-Tim-3 monoclonal antibody [23] were a kind gift of Dr. Luca Varani.…”

Section: Methodsmentioning

confidence: 99%

Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells

et al. 2016

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Acute myeloid leukaemia (AML) is a blood cancer affecting cells of myeloid lineage. It is characterised by rapid growth of malignant leukocytes that accumulate in the bone marrow and suppress normal haematopoiesis. This systemic disease remains a serious medical burden worldwide. Characterisation of protein antigens specifically expressed by malignant cells, but not by healthy leukocytes, is vital for the diagnostics and targeted treatment of AML. Here we report, for the first time, that the neuronal receptor latrophilin-1 is expressed in human monocytic leukaemia cell lines and in primary human AML cells. However, it is absent in healthy leukocytes. Latrophilin-1 is functional in leukaemia cells tested, and its biosynthesis is controlled through the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways. Our findings demonstrate that latrophilin-1 could be considered as a novel biomarker of human AML, which offers potential new avenues for AML diagnosis and treatment.

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Prediction of Epitopes in Closely Related Proteins Using a New Algorithm

Cited by 8 publications

References 10 publications

The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones

Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells

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