Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59597Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 馬徹(Che Ma) | |
| dc.contributor.author | Chia-Lin Chen | en |
| dc.contributor.author | 陳加林 | zh_TW |
| dc.date.accessioned | 2021-06-16T09:29:24Z | - |
| dc.date.available | 2027-03-24 | |
| dc.date.copyright | 2017-06-12 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-03-24 | |
| dc.identifier.citation | 1 Reichert, J. M. Marketed therapeutic antibodies compendium. MAbs 4, 413-415, (2012).
2 Vidarsson, G., Dekkers, G. & Rispens, T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5, 520, (2014). 3 Quast, I. & Lunemann, J. D. Fc glycan-modulated immunoglobulin G effector functions. J Clin Immunol 34 Suppl 1, S51-55, (2014). 4 Le, N. P., Bowden, T. A., Struwe, W. B. & Crispin, M. Immune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies. Biochim Biophys Acta 1860, 1655-1668, (2016). 5 Yu, X., Vasiljevic, S., Mitchell, D. A., Crispin, M. & Scanlan, C. N. Dissecting the molecular mechanism of IVIg therapy: the interaction between serum IgG and DC-SIGN is independent of antibody glycoform or Fc domain. J Mol Biol 425, 1253-1258, (2013). 6 Anthony, R. M., Wermeling, F., Karlsson, M. C. & Ravetch, J. V. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci U S A 105, 19571-19578, (2008). 7 Sondermann, P., Pincetic, A., Maamary, J., Lammens, K. & Ravetch, J. V. General mechanism for modulating immunoglobulin effector function. Proc Natl Acad Sci U S A 110, 9868-9872, (2013). 8 Diebolder, C. A. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260-1263, (2014). 9 Caaveiro, J. M., Kiyoshi, M. & Tsumoto, K. Structural analysis of Fc/FcgammaR complexes: a blueprint for antibody design. Immunol Rev 268, 201-221, (2015). 10 Woof, J. M. & Burton, D. R. Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 4, 89-99, (2004). 11 Bruhns, P. & Jonsson, F. Mouse and human FcR effector functions. Immunol Rev 268, 25-51, (2015). 12 Jiang, K. et al. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol 1, 419-425, (2000). 13 Perussia, B. Signaling for cytotoxicity. Nat Immunol 1, 372-374, (2000). 14 Clynes, R. A., Towers, T. L., Presta, L. G. & Ravetch, J. V. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6, 443-446, (2000). 15 Ying, T., Ju, T. W., Wang, Y., Prabakaran, P. & Dimitrov, D. S. Interactions of IgG1 CH2 and CH3 Domains with FcRn. Front Immunol 5, 146, (2014). 16 Jefferis, R. & Lund, J. Interaction sites on human IgG-Fc for FcgammaR: current models. Immunol Letters 82, 57-65 (2002). 17 Goebl, N. A. et al. Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells. Mol Biol Cell 19, 5490-5505, (2008). 18 Rath, T. et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol 35, 235-254, (2015). 19 Collin, M., Shannon, O. & Bjorck, L. IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions. Proc Natl Acad Sci U S A 105, 4265-4270, (2008). 20 Dalziel, M., Crispin, M., Scanlan, C. N., Zitzmann, N. & Dwek, R. A. Emerging principles for the therapeutic exploitation of glycosylation. Science 343, 1235681, (2014). 21 Zou, G. et al. Chemoenzymatic synthesis and Fcgamma receptor binding of homogeneous glycoforms of antibody Fc domain. Presence of a bisecting sugar moiety enhances the affinity of Fc to FcgammaIIIa receptor. J Am Chem Soc 133, 18975-18991, (2011). 22 Shields, R. L. et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem 277, 26733-26740, (2002). 23 Okazaki, A. et al. Fucose depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between IgG1 and FcgammaRIIIa. J Mol Biol 336, 1239-1249, (2004). 24 Huhn, C., Selman, M. H., Ruhaak, L. R., Deelder, A. M. & Wuhrer, M. IgG glycosylation analysis. Proteomics 9, 882-913, (2009). 25 Anthony, R. M. et al. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320, 373-376, (2008). 26 Liu, L. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci 104, 1866-1884, (2015). 27 Sha, S., Agarabi, C., Brorson, K., Lee, D. Y. & Yoon, S. N-Glycosylation Design and Control of Therapeutic Monoclonal Antibodies. Trends Biotechnol, 1360, 12 (2016). 28 Huang, W., Giddens, J., Fan, S. Q., Toonstra, C. & Wang, L. X. Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions. J Am Chem Soc 134, 12308-12318, (2012). 29 Krista Witte , P. S., Richard Martin , and Chi-Huey Wong Enzymatic Glycoprotein Synthesis: Preparation of Ribonuclease Glycoforms via Enzymatic Glycopeptide Condensation and Glycosylation. J Am Chem Soc 119, 2114-2118, (1997). 30 Lin, C. W. et al. A common glycan structure on immunoglobulin G for enhancement of effector functions. Proc Natl Acad Sci U S A 112, 10611-10616, (2015). 31 Teplyakov, A., Zhao, Y., Malia, T. J., Obmolova, G. & Gilliland, G. L. IgG2 Fc structure and the dynamic features of the IgG CH2-CH3 interface. Mol Immunol 56, 131-139, (2013). 32 Smith, P., DiLillo, D. J., Bournazos, S., Li, F. & Ravetch, J. V. Mouse model recapitulating human Fcgamma receptor structural and functional diversity. Proc Natl Acad Sci U S A 109, 6181-6186, (2012). 33 Ahmed, A. A., Keremane, S. R., Vielmetter, J. & Bjorkman, P. J. Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcgammaRIIIa. J Struct Biol 194, 78-89, (2016). 34 Ferrara, C. et al. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc Natl Acad Sci U S A 108, 12669-12674, (2011). 35 Ahmed, A. A. et al. Structural characterization of anti-inflammatory immunoglobulin G Fc proteins. J Mol Biol 426, 3166-3179, (2014). 36 Mizushima, T. et al. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells 16, 1071-1080, (2011). 37 Nimmerjahn, F. & Ravetch, J. V. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310, 1510-1512, (2005). 38 Barb, A. W. & Prestegard, J. H. NMR analysis demonstrates immunoglobulin G N-glycans are accessible and dynamic. Nat Chem Biol 7, 147-153, (2011). 39 Hanson, Q. M. & Barb, A. W. A perspective on the structure and receptor binding properties of immunoglobulin G Fc. Biochemistry 54, 2931-2942, (2015). 40 Raju, T. S. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol 20, 471-478, (2008). 41 Krapp, S., Mimura, Y., Jefferis, R., Huber, R. & Sondermann, P. Structural Analysis of Human IgG-Fc Glycoforms Reveals a Correlation Between Glycosylation and Structural Integrity. J Mol Biol 325, 979-989, (2003). 42 Crispin, M., Yu, X. & Bowden, T. A. Crystal structure of sialylated IgG Fc: implications for the mechanism of intravenous immunoglobulin therapy. Proc Natl Acad Sci U S A 110, E3544-3546, (2013). 43 Barb, A. W. et al. NMR characterization of immunoglobulin G Fc glycan motion on enzymatic sialylation. Biochemistry 51, 4618-4626, (2012). 44 Yu, X. et al. Engineering hydrophobic protein-carbohydrate interactions to fine-tune monoclonal antibodies. J Am Chem Soc 135, 9723-9732, (2013). 45 Raju, T. S. & Lang, S. E. Diversity in structure and functions of antibody sialylation in the Fc. Curr Opin Biotechnol 30, 147-152, (2014). 46 Chen, W. et al. Stabilizing the CH2 Domain of an Antibody by Engineering in an Enhanced Aromatic Sequon. ACS Chem Biol (2016). 47 Reeves, P. J., Callewaert, N., Contreras, R. & Khorana, H. G. Structure and function in rhodopsin: high-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible N-acetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line. Proc Natl Acad Sci U S A 99, 13419-13424, (2002). 48 Jiang, N. et al. Effects of anchor structure and glycosylation of Fcgamma receptor III on ligand binding affinity. Mol Biol Cell 27, 3449-3458, (2016). 49 Wu, J. et al. A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 100, 1059-1070, (1997). 50 Koene, H. R. et al. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood 90, 1109-1114 (1997). 51 Mellor, J. D., Brown, M. P., Irving, H. R., Zalcberg, J. R. & Dobrovic, A. A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer. J Hematol Oncol 6, 1, (2013). 52 Kim, D. H. et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood 108, 2720-2725, (2006). 53 Liu, F. et al. FCGR3A 158V/F polymorphism and response to frontline R-CHOP therapy in diffuse large B-cell lymphoma. DNA Cell Biol 33, 616-623, (2014). 54 Johnson, D. E., Ostrowski, P., Jaumouille, V. & Grinstein, S. The position of lysosomes within the cell determines their luminal pH. J Cell Biol 212, 677-692, (2016). 55 Qiu, X. et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514, 47-53, (2014). 56 Lee, J. E. et al. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 454, 177-182, (2008). 57 Murin, C. D. et al. Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci U S A 111, 17182-17187, (2014). 58 DiLillo, D. J., Tan, G. S., Palese, P. & Ravetch, J. V. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Nat Med 20, 143-151, (2014). 59 Chapman, H. N. et al. Femtosecond X-ray protein nanocrystallography. Nature 470, 73-77, (2011). 60 Wang, J. Destruction-and-diffraction by X-ray free-electron laser. Protein Sci 25, 1585-1592, (2016). 61 Kupitz, C. et al. Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser. Nature 513, 261-265, (2014). 62 Young, I. D. et al. Structure of photosystem II and substrate binding at room temperature. Nature 540, 453-457, (2016). 63 Hirata, K. et al. Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nat Methods 11, 734-736, (2014). 64 Joti, Y. et al. Data acquisition system for X-ray free-electron laser experiments at SACLA. J Synchrotron Radiat 22, 571-576, (2015). 65 Wang, C. et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res 2, 846-856, (2014). 66 Chen, W. et al. Structural and energetic basis of carbohydrate-aromatic packing interactions in proteins. J Am Chem Soc 135, 9877-9884, (2013). 67 Zbyszek Otwinowski, W. M. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276, 307-326 (1997). 68 Matthews, B. W. Solvent content of protein crystals. J Mol Biol 33, 491-497 (1968). 69 Kantardjieff, K. A. & Rupp, B. Matthews coefficient probabilities: Improved estimates for unit cell contents of proteins, DNA, and protein-nucleic acid complex crystals. Protein Sci 12, 1865-1871, (2003). 70 McCoy, A. J. et al. Phaser crystallographic software. J Appl Crystallogr 40, 658-674, (2007). 71 Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213-221, (2010). 72 Paul Emsley, K. C. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126-2132 (2004). 73 Lutteke, T. & von der Lieth, C. W. pdb-care (PDB carbohydrate residue check): a program to support annotation of complex carbohydrate structures in PDB files. BMC bioinformatics 5, 69, (2004). 74 Lutteke, T., Frank, M. & von der Lieth, C. W. Carbohydrate Structure Suite (CSS): analysis of carbohydrate 3D structures derived from the PDB. Nucleic Acids Res 33, D242-246, (2005). 75 Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 1.8 (2015). 76 Yu, Y. et al. Understanding ForteBio's Sensors for High-Throughput Kinetic and Epitope Screening for Purified Antibodies and Yeast Culture Supernatant. J Biomol Screen 21, 88-95, (2016). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59597 | - |
| dc.description.abstract | N-醣基化會影響抗體免疫球蛋白Ｇ中，Fc部位的結構和效用功能。若免疫球蛋白Ｇ經由人為的酵素優化後，使其帶有人類唾液酸複合型醣 (hSCT) 修飾，會增強此種抗體對於Fc第三Ａ型受器的親和力並使修飾後的抗體具有更強的抗體依賴性細胞媒介毒殺作用。hSCT在結構上具有雙延伸支鏈，兩條支鏈的尾端都是alpha-2,6連結的唾液酸，且沒有岩藻醣基化。hSCT修飾後的抗體不僅能在抗原結合的狀況下增強對Fc受器的親和力，更能使某些本來不具抗體依賴性細胞媒介毒殺作用的抗體獲得此新功能。我們利用酵素優化大量的免疫球蛋白G抗體使其帶有hSCT修飾，並利用x光繞射結晶學方法解析其Fc部位的立體解構到1.85 Å的解析度。在此結構中我們發現同時存在一個閉鎖型和一個開放型的構形：在閉鎖型中， hSCT醣鏈利用醣分子間的作用形成兩處結合點，以穩定此閉鎖型的結構；在開放型中，hSCT醣鏈尾端的唾液酸會利用水分子間接結合免疫球蛋白上的D249-L251位置，並藉此調控抗體CH2和CH3部位的相對位置。這是第一個Fc部位帶有能增進抗體依賴性細胞媒介毒殺作用活性的醣基化修飾其立體結構被解析出來。此研究不僅解釋了免疫球蛋白G中Fc部位被hSCT修飾後，蛋白質結構彈性和效用功能間的關係，並為後續臨床抗體修飾工程提供重要的資訊。 | zh_TW |
| dc.description.abstract | N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG contains a human sialo-complex type (hSCT) glycan of biantennary structure with two alpha-2,6-sialylations and without core-fucosylation is an optimized glycoform developed to targeting FcRIIIA and enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. Binding kinetics analysis indicated the increased affinity to both alleles of FcRIIIA is mainly due to a 10-fold decrease of off rate. In addition, ADCC activity assay suggested IgGhSCT provides better killing effect no matter the targeted antigens are viral or tumor-related molecules.
IgG-Fc with homogeneous hSCT attached to each CH2 domain was prepared by enzymatic glyco-engineering, and its crystal structure was solved in 1.85 Å resolution. A compact form and an open form were observed in the crystal. In the compact structure, the double glycan latches from the two hSCT chains stabilize the CH2 domains in a closed conformation. In the open structure, the terminal sialic acid residue interacts through water-mediated hydrogen bonds with the D249-L251 helix, to modulate the pivot region of CH2-CH3 interface. This is the first crystal structure of glyco-engineered Fc with enhanced effector activities. A structure-based engineering of IgG together with the hSCT modification were designed to provide even better ADCC and immune protecting effect. In addition, the structural studies of intact immune complex which includes IgGhSCT/antigen/FcRIIIA was conducted by x-ray crystallography and cryo-EM method. This work provides insights into the relationship between the structural stability and effector functions affected by hSCT modification and the development of better antibodies for therapeutic applications. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T09:29:24Z (GMT). No. of bitstreams: 1 ntu-106-D98b46015-1.pdf: 6982408 bytes, checksum: 562bf80ffa4138f38190311711c463de (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 中文摘要 I
Abstract II Abbreviations IV I. Introduction 1 1.1 Immunoglobulin G 1 1.2 Effector functions and receptors of IgG 2 1.3 N-glycosylation and glyco-engineering of IgG 4 II. Results and Discussion 7 2.1 Crystal structure of FchSCT 7 2.1.1 Structure of two forms of FchSCT 7 2.1.2 Structure comparison of FchSCT with other Fc glycoforms 8 2.1.3 Double glycan latches in FchSCT dimer 10 2.1.4 Terminal sialic acid residue interacts with the pivot region of Fc 11 2.1.5 hSCT glycan modulates the conformational plasticity of Fc 12 2.2 Binding affinity of IgGhSCT to Fc receptors 15 2.2.1 Polymorphism of FcRIIIA: V158 and F158 15 2.2.2 hSCT modification enhances the Fc receptor binding avidity of antigen-IgG complex 17 2.2.3 Binding affinity of IgGhSCT to FcRIA, IIA, IIB, and IIIB 18 2.2.4 Binding affinity of IgGhSCT to neonatal Fc receptor 19 2.3 Enhanced ADCC activity of IgGhSCT 20 2.3.1 IgGhSCT enhances ADCC activity: ZMapp 20 2.3.2 ADCC activity of IgGhSCT to endogenous antigen 21 2.3.3 Live imaging of ADCC 22 2.4 Structure-based engineering of IgGhSCT 24 2.4.1 Rational design of D249 mutant 24 2.4.2 Binding affinity of D249 mutants to FcRIIIA 24 2.5 XFEL study of FchSCT 25 2.6 Ternary complex of IgGhSCT/antigen/FcRIIIA 26 2.6.1 Ternary complex formation of trastuzumabhSCT/HER2/ FcRIIIA 26 2.6.2 X-ray data collection of ternary complex crystal 28 2.6.3 Grid screening of ternary complex 28 III. Conclusion 30 IV. Methods and Materials 34 4.1 Antibody expression and purification 34 4.2 Protein expression and purification of Fc receptors and HER2 34 4.3 Preparation of homogenous glycoform IgGhSCT or FchSCT 35 4.4 Crystallization and data collection of FchSCT 36 4.5 Structural determination of FchSCT 37 4.6 Bio-layer interferometry (BLI) analysis 37 4.7 Antibody dependent cellular cytotoxicity (ADCC) assay 38 4.8 Live imaging of ADCC 39 4.9 XFEL data collection of FchSCT crystal 40 4.10 Ternary complex formation 40 4.11 Crystallization screening and data collection of ternary complex crystal 41 V. References 43 VI. Tables 52 Table 1. Data collection and refinement statistics 52 Table 2. Construct list of Fc receptors and nFcR 53 Table 3. Binding affinity between IgGs and FcRIIIA with different glycan lengths 55 Table 4. Binding affinity between IgGs and different allelic FcRIIIA 56 Table 5. Binding affinity between IgGs and Fc receptors 57 Table 6. Binding affinity between IgGs and nFcR 58 Table 7. Binding affinity between ZMapp, KZ52 and FcRIIIA 59 Table 8. Binding affinity between IgG D249 mutants and FcRIIIA 60 Table 9. Data collection statistics of XFEL 61 Table 10. Data collection statistics of ternary complex 62 Table 11. List of precipitates for grid screening 63 Table 12. List of buffers for grid screening 64 Table 13. List of salts for grid screening 66 VII. Figures 68 Figure 1. Structure of IgG and N297-linked glycan 68 Figure 2. Mechanism of antibody dependent cellular cytotoxicity 69 Figure 3. Two forms of FchSCT structure 70 Figure 4. Superimposition of two forms of FchSCT structure 71 Figure 5. Alignment of FchSCT with Fc containing different glycoforms or mutations. 72 Figure 6. Alignment of FchSCT with Fc in complex with FcRIIIA. 73 Figure 7. Alignment of FchSCT with two forms of di-sialylated, fucosylated Fc: 74 Figure 8. Glycan structures in electron density map of FchSCT 75 Figure 9. Two glycan-glycan interaction sites in compact FchSCT 76 Figure 10. Glycan-glycan interaction networks in compact FchSCT 77 Figure 11. Protein-glycan interaction networks in FchSCT 78 Figure 12. Interactions near the terminal sialic acid residue and pivot region between CH2 and CH3 domains 79 Figure 13. Modeled states of FchSCT structure 80 Figure 14. BLI analysis of glyco-engineered antibody, with or without a bound antigen, binding to FcRIIIA 81 Figure 15. Purified antibodies of ZMapp and KZ52 82 Figure 16. Flow cytometry analysis of antibody binding to Ebola GP protein 83 Figure 17. ADCC assay of native IgG and IgGhSCT 84 Figure 18. ADCC assay of trastuzumab and trastuzumabhSCT against cancer cells 85 Figure 19. Live imaging of ADCC assay 86 Figure 20. Structure-based engineering of IgGhSCT 87 Figure 21. XFEL exposure of FchSCT crystal 88 Figure 22. N-glycosylation site mutants of FcRIIIA 90 Figure 23. Truncated mutant of FcRIIIAN38QN74QN169Q 91 Figure 24. Complex formation of FchSCT and FcRIIIA truncated mutant 92 Figure 25. Ternary complex formation of trastuzumabhSCT/HER2/FcRIIIA 93 Figure 26. Ternary complex formation of rituximabhSCT/CD20 peptide/FcRIIIA 94 Figure 27. Protein crystal of ternary complex 95 Figure 28. SDS-PAGE staining of purified Fc receptors 96 Figure 29. Purification of FchSCT 97 Figure 30. Characterization of FchSCT 99 Figure 31. X-ray diffraction of FchSCT crystal 100 Figure 32. Flow chart of structural determination of FchSCT 101 Appendix 102 | |
| dc.language.iso | en | |
| dc.subject | 免疫複合體 | zh_TW |
| dc.subject | 抗體Fc結構 | zh_TW |
| dc.subject | 醣基化修飾 | zh_TW |
| dc.subject | 抗體依賴性細胞媒介毒殺作用 | zh_TW |
| dc.subject | Fc受器 | zh_TW |
| dc.subject | 免疫複合體 | zh_TW |
| dc.subject | 抗體Fc結構 | zh_TW |
| dc.subject | 醣基化修飾 | zh_TW |
| dc.subject | Fc受器 | zh_TW |
| dc.subject | 抗體依賴性細胞媒介毒殺作用 | zh_TW |
| dc.subject | Fc receptor | en |
| dc.subject | glyco-engineered antibody | en |
| dc.subject | Fc structure | en |
| dc.subject | immune complex | en |
| dc.subject | antibody dependent cellular cytotoxicity | en |
| dc.subject | glyco-engineered antibody | en |
| dc.subject | Fc structure | en |
| dc.subject | immune complex | en |
| dc.subject | Fc receptor | en |
| dc.subject | antibody dependent cellular cytotoxicity | en |
| dc.title | 醣基化修飾抗體與抗體受器複合體之結構研究 | zh_TW |
| dc.title | Structural studies of glyco-engineered IgG/Fc receptor complex | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 林俊宏 | |
| dc.contributor.oralexamcommittee | 林國儀,吳宗益,傅琪鈺 | |
| dc.subject.keyword | 醣基化修飾,抗體Fc結構,免疫複合體,Fc受器,抗體依賴性細胞媒介毒殺作用, | zh_TW |
| dc.subject.keyword | glyco-engineered antibody,Fc structure,immune complex,Fc receptor,antibody dependent cellular cytotoxicity, | en |
| dc.relation.page | 131 | |
| dc.identifier.doi | 10.6342/NTU201700712 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-03-27 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| Appears in Collections: | 生化科學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-106-1.pdf Restricted Access | 6.82 MB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.