可变淋巴细胞受体:一种新型的恶性肿瘤诊断治疗试剂
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摘要
可变淋巴细胞受体(variable lymphocyte receptor,VLR)是2004年于无颌类脊椎动物七鳃鳗(Lampetra japonicum)中发现的一种新型受体。VLR具有分子结构简单、识别抗原种类广泛、对蛋白质和聚糖的结合特异性强且亲和力高、化学性质稳定等多方面优点。研究表明,VLR可识别表达于腺癌和鳞状细胞癌等细胞表面的碳水化合物,以及多发性骨髓瘤浆细胞表面的特异性标志物。VLR经改造后构建的重组分子可用于恶性肿瘤的成像、诊断和治疗。近年来,VLR在抗肿瘤免疫反应中的作用及以其作为疫苗的研究不断深入。本文对VLR研究的最新进展进行综述,以期为进一步的药物开发及临床研究等提供参考。
Variable lymphocyte receptor( VLR) is a novel receptor found in the jawless vertebrate Lampetra japonicum in 2004. VLR has many advantages such as simple molecular structure,wide variety of antigen recognition,strong binding specificity,high affinity and chemical stability to protein and polysaccaride. Studies have shown that VLR can recognize carbohydrates expressed on the surface of cells of adenocarcinoma and squamous cell carcinoma. VLR can also recognize specific markers on the surface of multiple myeloma plasma cells. Recombinant molecules composed of VLR can be used for imaging,diagnosis and treatment of malignant tumors. In recent years,the significance of VLR in anti-tumor immune response and research of VLR as a vaccine has expanded. In this paper,we review the latest research progress of VLR,which hopefully will provide a reference for further drug development and clinical research.
Variable lymphocyte receptor( VLR) is a novel receptor found in the jawless vertebrate Lampetra japonicum in 2004. VLR has many advantages such as simple molecular structure,wide variety of antigen recognition,strong binding specificity,high affinity and chemical stability to protein and polysaccaride. Studies have shown that VLR can recognize carbohydrates expressed on the surface of cells of adenocarcinoma and squamous cell carcinoma. VLR can also recognize specific markers on the surface of multiple myeloma plasma cells. Recombinant molecules composed of VLR can be used for imaging,diagnosis and treatment of malignant tumors. In recent years,the significance of VLR in anti-tumor immune response and research of VLR as a vaccine has expanded. In this paper,we review the latest research progress of VLR,which hopefully will provide a reference for further drug development and clinical research.
引文
[1]吴艳红,王慧茹,邓振领,等.肿瘤生物免疫治疗研究进展[J].科技导报(Wu YH,Wang HR,Deng ZL,et al.Progress in cancer bio-immunotherapy[J].Sci Technol Rev),2014,32(26):27-36
[2]Li S,Schmitz KR,Jeffrey PD,et al.Structural basis for inhibition of the epidermal growth factor receptor by cetuximab[J].Cancer Cell,2005,7(4):301-311
[3]Kay BP,Hsu CP,Lu JF,et al.Intracellular-signaling tumorregression modeling of the pro-apoptotic receptor agonists dulanermin and conatumumab[J].J Pharmacokinet Pharmacodyn,2012,39(5):577-590
[4]Collett L,Howard DR,Munir T,et al.Assessment of ibrutinib plus rituximab in front-line CLL(FLAIR trial):study protocol for a phase III randomised controlled trial[J].Trials,2017,18(1):387
[5]Meyer A,Zardoya R.Recent advances in the(molecular)phylogeny of vertebrates[J].Annu Rev Ecol Evol Syst,2003,34:311-338
[6]Takezaki N,Figueroa F,Zaleska-Rutczynska Z,et al.Molecular phylogeny of early vertebrates:monophyly of the agnathans as revealed by sequences of 35 genes[J].Mol Biol Evol,2003,20(2):287-292
[7]Pancer Z,Amemiya CT,Ehrhardt GR,et al.Somatic diversication of variable lymphocyte receptors in the agnathan sea lamprey[J].Nature,2004,430(6996):174-180
[8]乔旭.日本七鳃鳗免疫方案的建立及抗血清杀伤活性的鉴定[D].辽宁师范大学(Qiao X.Establishment of immunization programme on Lampetra japonica and cytolytic effects assay of antiserum[D].Liaoning Normal University),2012
[9]吴芬芳,马宁,陈立勇,等.日本七鳃鳗(Lampetra japonica)VLRB的克隆表达及单克隆抗体制备[J].遗传(Wu FF,Ma N,Chen LY,et al.Cloning and expression of VLRB of Lampetra japonica and generation of the corresponding monoclonal antibodies[J].Hereditas),2012,34(4):465-471
[10]于涛,韩英伦,肖蓉,等.临床诊断与治疗的新工具-可变淋巴细胞受体[J].遗传(Yu T,Han YL,Xiao R,et al.Variable lymphocyte receptors:the novel tool for clinical diagnosis and therapy[J].Hereditas),2013,35(1):55-61
[11]Collins BC,Nakahara H,Acharya S,et al.Crystal structure of an anti-idiotype variable lymphocyte receptor[J].Acta Crystallogr F Struct Biol Commun,2017,73(Pt 12):682-687
[12]Nakahara H,Herrin BR,Alder MN,et al.Chronic lymphocytic leukemia monitoring with a Lamprey idiotope-specific antibody[J].Cancer Immunol Res,2013,1(4):223-228
[13]Gunn RJ,Herrin BR,Acharya S,et al.VLR recognition of TLR5 expands the molecular characterization of protein antigen binding by non-Ig-based antibodies[J].J Mol Biol,2018,430(9):1350-1367
[14]潘雄.重组七鳃鳗VLRB蛋白功能的初步研究[D].辽宁师范大学(Pan X.The preliminary research on the restructuring lampreys VLRB protein function[D].Liaoning Normal University),2016
[15]Rogozin IB,Iyer LM,Liang L,et al.Evolution and diversification of lamprey antigen receptors:evidence for involvement of an AID-APOBEC family cytosine deaminase[J].Nat Immunol,2007,8(6):647-656
[16]Nagawa F,Kishishita N,Shimizu K,et al.Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice[J].Nat Immunol,2007,8(2):206-213
[17]Alder MN,Rogozin IB,Iyer LM,et al.Diversity and function of adaptive immune receptors in a jawless vertebrate[J].Science,2005,310(5756):1970-1973
[18]Boehm T,Hirano M,Holland SJ,et al.Evolution of alternative adaptive immune systems in vertebrates[J].Annu Rev Immunol,2018,36:19-42
[19]Kim HM,Oh SC,Lim KJ,et al.Structural diversity of the hagfish variable lymphocyte receptors[J].J Biol Chem,2007,282(9):6726-6732
[20]梁佼,刘欣,吴芬芳,等.无颌类脊椎动物适应性免疫系统的研究进展[J].遗传(Liang J,Liu X,Wu FF,et al.Progress of adaptive immunity system of agnathan vertebrates[J].Hereditas),2009,31(10):969-976
[21]Alder MN,Herrin BR,Sadlonova A,et al.Antibody responses of variable lymphocyte receptors in the lamprey[J].Nat Immunol,2008,9(3):319-327
[22]Boehm T,Mc Curley N,Sutoh Y,et al.VLR-based adaptive immunity[J].Annu Rev Immunol,2012,30:203-220
[23]Wezner-Ptasińska M,Krowarsch D,Otlewski J.Design and characteristics of a stable protein scaffold for specific binding based on variable lymphocyte receptor sequences[J].Biochim Biophys Acta,2011,1814(9):1140-1145
[24]Lee JS,Kim J,Im SP,et al.Expression and characterization of monomeric variable lymphocyte receptor B specific to the glycoprotein of viral hemorrhagic septicemia virus(VHSV)[J].J Immunol Methods,2018,462:48-53
[25]Pancer Z,Saha NR,Kasamatsu J,et al.Variable lymphocyte receptors in hagfish[J].Proc Natl Acad Sci USA,2005,102(26):9224-9229
[26]Kasamatsu J,Sutoh Y,Fugo K,et al.Identification of a third variable lymphocyte receptor in the lamprey[J].Proc Natl Acad Sci USA,2010,107(32):14304-14308
[27]Han BW,Herrin BR,Cooper MD,et al.Antigen recognition by variable lymphocyte receptors[J].Science,2008,321(5897):1834-1837
[28]Velikovsky CA,Deng L,Tasumi S,et al.Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen[J].Nat Struct Mol Biol,2009,16(7):725-730
[29]Deng L,Velikovsky CA,Xu G,et al.A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey[J].Proc Natl Acad Sci USA,2010,107(30):13408-13413
[30]易濒,张敏,Schwartz-Albiez R,等.Thomsen-Friedenreich抗原(TF,CD176)抗体诱导人类白血病细胞凋亡的机制研究[C].中国细胞生物学学会全体会员代表大会暨第十二次学术大会(Yi B,Zhang M,Schwartz-Albiez R,et al.Mechanism of Thomsen-Friedenreich Antigen(TF,CD176)Antibody Inducing Apoptosis of Human Leukemia Cells[C].All member congresses and the twelfth academic conference of Chinese Society for Cell Biology),2011
[31]罗铭.酿酒酵母谷氧还蛋白Grx6与七鳃鳗免疫受体VLRB的结构与功能研究[D].中国科学技术大学(Luo M.Structural and functional study of yeast glutaredoxin Grx6 and lamprey immune receptor VLRB[D].University of Science and Technology of China),2013
[32]Luo M,Velikovsky CA,Yang X,et al.Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor[J].J Biol Chem,2013,288(32):23597-23606
[33]Waters EA,Shusta EV.The variable lymphocyte receptor as an antibody alternative[J].Curr Opin Biotechnol,2018,52:74-79
[34]Meissner M,Reichert TE,Kunkel M,et al.Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma:association with clinical outcome[J].Clin Cancer Res,2005,11(7):2552-2560
[35]Seliger B,Atkins D,Bock M,et al.Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation[J].Clin Cancer Res,2003,9(5):1721-1727
[36]Chan JTH,Liu Y,Khan S,et al.A tyrosine sulfation-dependent HLA-I modification identifies memory B cells and plasma cells[J].Sci Adv,2018,4(11):1-11
[37]Yu C,Liu Y,Chan JTH,et al.Identification of human plasma cells with a lamprey monoclonal antibody[J].JCI Insight,2016,1(3).pii:84738
[38]Yun M,Kim DY,Lee JJ,et al.A high-affinity repebody for molecular imaging of EGFR-expressing malignant tumors[J].Theranostics,2017,7(10):2620-2633
[39]Pyo A,Yun M,Kim HS,et al.64Cu-labeled repebody molecules for imaging of epidermal growth factor receptor-expressing tumors[J].J Nucl Med,2018,59(2):340-346
[40]Lee JJ,Kim HJ,Yang CS,et al.A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer[J].Mol Ther,2014,22(7):1254-1265
[41]Lee JJ,Kang JA,Ryu Y,et al.Genetically engineered and selfassembled oncolytic protein nanoparticles for targeted cancer therapy[J].Biomaterials,2017,120:22-31
[42]Hwang DE,Ryou JH,Oh JR,et al.Anti-human VEGF repebody effectively suppresses choroidal neovascularization and vascular leakage[J].PLoS One,2016,11(3):e0152522
[43]魏建树,韩为东.CAR-T细胞治疗实体肿瘤:且行且思考[J].中国肿瘤生物治疗杂志(Wei JS,Han WD.CAR-T cell treatment of solid tumors:thoughts and practice[J].Chin JCancer Biother),2018,25(9):847-853
[44]Moot R,Raikar SS,Fleischer L,et al.Genetic engineering of chimeric antigen receptors using lamprey derived variable lymphocyte receptors[J].Mol Ther Oncolytics,2016,3:16026
[45]Lee SC,Park K,Han J,et al.Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering[J].Proc Natl Acad Sci USA,2012,109(9):3299-3304
[46]Lee JJ,Choi HJ,Yun M,et al.Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy[J].Angew Chem Int Ed Engl,2015,54(41):12020-12024
[47]Collins BC,Gunn RJ,Mckitrick TR,et al.Structural insights into VLR fine specificity for blood group carbohydrates[J].Structure,2017,25(11):1667-1678
[48]Saupe F,Reichel M,Huijbers EJ,et al.Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously[J].FASEB J,2017,31(3):1204-1214
[49]Kim HY,Lee JJ,Kim N,et al.Tracking protein-protein interaction and localization in living cells using a high-affinity molecular binder[J].Biochem Biophys Res Commun,2016,470(4):857-863
[50]Velásquez AC,Nomura K,Cooper MD,et al.Leucine-richrepeat-containing variable lymphocyte receptors as modules to target plant-expressed proteins[J].Plant Methods,2017,13:29
[51]Paatero A,Rosti K,Shkumatov AV,et al.Crystal structure of an engineered LRRTM2 synaptic adhesion molecule and a model for neurexin binding[J].Biochemistry,2016,55(6):914-926
[52]Kim HM,Park BS,Kim JI,et al.Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran[J].Cell,2007,130(5):906-917
[53]Lee JS,Kim J,Im SP,et al.Generation and characterization of hagfish variable lymphocyte receptor B against glycoprotein of viral hemorrhagic septicemia virus(VHSV)[J].Mol Immunol,2018,99:30-38
[54]Herrin BR,Alder MN,Roux KH,et al.Structure and specificity of lamprey monoclonal antibodies[J].Proc Natl Acad Sci USA,2008,105(6):2040-2045
[2]Li S,Schmitz KR,Jeffrey PD,et al.Structural basis for inhibition of the epidermal growth factor receptor by cetuximab[J].Cancer Cell,2005,7(4):301-311
[3]Kay BP,Hsu CP,Lu JF,et al.Intracellular-signaling tumorregression modeling of the pro-apoptotic receptor agonists dulanermin and conatumumab[J].J Pharmacokinet Pharmacodyn,2012,39(5):577-590
[4]Collett L,Howard DR,Munir T,et al.Assessment of ibrutinib plus rituximab in front-line CLL(FLAIR trial):study protocol for a phase III randomised controlled trial[J].Trials,2017,18(1):387
[5]Meyer A,Zardoya R.Recent advances in the(molecular)phylogeny of vertebrates[J].Annu Rev Ecol Evol Syst,2003,34:311-338
[6]Takezaki N,Figueroa F,Zaleska-Rutczynska Z,et al.Molecular phylogeny of early vertebrates:monophyly of the agnathans as revealed by sequences of 35 genes[J].Mol Biol Evol,2003,20(2):287-292
[7]Pancer Z,Amemiya CT,Ehrhardt GR,et al.Somatic diversication of variable lymphocyte receptors in the agnathan sea lamprey[J].Nature,2004,430(6996):174-180
[8]乔旭.日本七鳃鳗免疫方案的建立及抗血清杀伤活性的鉴定[D].辽宁师范大学(Qiao X.Establishment of immunization programme on Lampetra japonica and cytolytic effects assay of antiserum[D].Liaoning Normal University),2012
[9]吴芬芳,马宁,陈立勇,等.日本七鳃鳗(Lampetra japonica)VLRB的克隆表达及单克隆抗体制备[J].遗传(Wu FF,Ma N,Chen LY,et al.Cloning and expression of VLRB of Lampetra japonica and generation of the corresponding monoclonal antibodies[J].Hereditas),2012,34(4):465-471
[10]于涛,韩英伦,肖蓉,等.临床诊断与治疗的新工具-可变淋巴细胞受体[J].遗传(Yu T,Han YL,Xiao R,et al.Variable lymphocyte receptors:the novel tool for clinical diagnosis and therapy[J].Hereditas),2013,35(1):55-61
[11]Collins BC,Nakahara H,Acharya S,et al.Crystal structure of an anti-idiotype variable lymphocyte receptor[J].Acta Crystallogr F Struct Biol Commun,2017,73(Pt 12):682-687
[12]Nakahara H,Herrin BR,Alder MN,et al.Chronic lymphocytic leukemia monitoring with a Lamprey idiotope-specific antibody[J].Cancer Immunol Res,2013,1(4):223-228
[13]Gunn RJ,Herrin BR,Acharya S,et al.VLR recognition of TLR5 expands the molecular characterization of protein antigen binding by non-Ig-based antibodies[J].J Mol Biol,2018,430(9):1350-1367
[14]潘雄.重组七鳃鳗VLRB蛋白功能的初步研究[D].辽宁师范大学(Pan X.The preliminary research on the restructuring lampreys VLRB protein function[D].Liaoning Normal University),2016
[15]Rogozin IB,Iyer LM,Liang L,et al.Evolution and diversification of lamprey antigen receptors:evidence for involvement of an AID-APOBEC family cytosine deaminase[J].Nat Immunol,2007,8(6):647-656
[16]Nagawa F,Kishishita N,Shimizu K,et al.Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice[J].Nat Immunol,2007,8(2):206-213
[17]Alder MN,Rogozin IB,Iyer LM,et al.Diversity and function of adaptive immune receptors in a jawless vertebrate[J].Science,2005,310(5756):1970-1973
[18]Boehm T,Hirano M,Holland SJ,et al.Evolution of alternative adaptive immune systems in vertebrates[J].Annu Rev Immunol,2018,36:19-42
[19]Kim HM,Oh SC,Lim KJ,et al.Structural diversity of the hagfish variable lymphocyte receptors[J].J Biol Chem,2007,282(9):6726-6732
[20]梁佼,刘欣,吴芬芳,等.无颌类脊椎动物适应性免疫系统的研究进展[J].遗传(Liang J,Liu X,Wu FF,et al.Progress of adaptive immunity system of agnathan vertebrates[J].Hereditas),2009,31(10):969-976
[21]Alder MN,Herrin BR,Sadlonova A,et al.Antibody responses of variable lymphocyte receptors in the lamprey[J].Nat Immunol,2008,9(3):319-327
[22]Boehm T,Mc Curley N,Sutoh Y,et al.VLR-based adaptive immunity[J].Annu Rev Immunol,2012,30:203-220
[23]Wezner-Ptasińska M,Krowarsch D,Otlewski J.Design and characteristics of a stable protein scaffold for specific binding based on variable lymphocyte receptor sequences[J].Biochim Biophys Acta,2011,1814(9):1140-1145
[24]Lee JS,Kim J,Im SP,et al.Expression and characterization of monomeric variable lymphocyte receptor B specific to the glycoprotein of viral hemorrhagic septicemia virus(VHSV)[J].J Immunol Methods,2018,462:48-53
[25]Pancer Z,Saha NR,Kasamatsu J,et al.Variable lymphocyte receptors in hagfish[J].Proc Natl Acad Sci USA,2005,102(26):9224-9229
[26]Kasamatsu J,Sutoh Y,Fugo K,et al.Identification of a third variable lymphocyte receptor in the lamprey[J].Proc Natl Acad Sci USA,2010,107(32):14304-14308
[27]Han BW,Herrin BR,Cooper MD,et al.Antigen recognition by variable lymphocyte receptors[J].Science,2008,321(5897):1834-1837
[28]Velikovsky CA,Deng L,Tasumi S,et al.Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen[J].Nat Struct Mol Biol,2009,16(7):725-730
[29]Deng L,Velikovsky CA,Xu G,et al.A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey[J].Proc Natl Acad Sci USA,2010,107(30):13408-13413
[30]易濒,张敏,Schwartz-Albiez R,等.Thomsen-Friedenreich抗原(TF,CD176)抗体诱导人类白血病细胞凋亡的机制研究[C].中国细胞生物学学会全体会员代表大会暨第十二次学术大会(Yi B,Zhang M,Schwartz-Albiez R,et al.Mechanism of Thomsen-Friedenreich Antigen(TF,CD176)Antibody Inducing Apoptosis of Human Leukemia Cells[C].All member congresses and the twelfth academic conference of Chinese Society for Cell Biology),2011
[31]罗铭.酿酒酵母谷氧还蛋白Grx6与七鳃鳗免疫受体VLRB的结构与功能研究[D].中国科学技术大学(Luo M.Structural and functional study of yeast glutaredoxin Grx6 and lamprey immune receptor VLRB[D].University of Science and Technology of China),2013
[32]Luo M,Velikovsky CA,Yang X,et al.Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor[J].J Biol Chem,2013,288(32):23597-23606
[33]Waters EA,Shusta EV.The variable lymphocyte receptor as an antibody alternative[J].Curr Opin Biotechnol,2018,52:74-79
[34]Meissner M,Reichert TE,Kunkel M,et al.Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma:association with clinical outcome[J].Clin Cancer Res,2005,11(7):2552-2560
[35]Seliger B,Atkins D,Bock M,et al.Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation[J].Clin Cancer Res,2003,9(5):1721-1727
[36]Chan JTH,Liu Y,Khan S,et al.A tyrosine sulfation-dependent HLA-I modification identifies memory B cells and plasma cells[J].Sci Adv,2018,4(11):1-11
[37]Yu C,Liu Y,Chan JTH,et al.Identification of human plasma cells with a lamprey monoclonal antibody[J].JCI Insight,2016,1(3).pii:84738
[38]Yun M,Kim DY,Lee JJ,et al.A high-affinity repebody for molecular imaging of EGFR-expressing malignant tumors[J].Theranostics,2017,7(10):2620-2633
[39]Pyo A,Yun M,Kim HS,et al.64Cu-labeled repebody molecules for imaging of epidermal growth factor receptor-expressing tumors[J].J Nucl Med,2018,59(2):340-346
[40]Lee JJ,Kim HJ,Yang CS,et al.A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer[J].Mol Ther,2014,22(7):1254-1265
[41]Lee JJ,Kang JA,Ryu Y,et al.Genetically engineered and selfassembled oncolytic protein nanoparticles for targeted cancer therapy[J].Biomaterials,2017,120:22-31
[42]Hwang DE,Ryou JH,Oh JR,et al.Anti-human VEGF repebody effectively suppresses choroidal neovascularization and vascular leakage[J].PLoS One,2016,11(3):e0152522
[43]魏建树,韩为东.CAR-T细胞治疗实体肿瘤:且行且思考[J].中国肿瘤生物治疗杂志(Wei JS,Han WD.CAR-T cell treatment of solid tumors:thoughts and practice[J].Chin JCancer Biother),2018,25(9):847-853
[44]Moot R,Raikar SS,Fleischer L,et al.Genetic engineering of chimeric antigen receptors using lamprey derived variable lymphocyte receptors[J].Mol Ther Oncolytics,2016,3:16026
[45]Lee SC,Park K,Han J,et al.Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering[J].Proc Natl Acad Sci USA,2012,109(9):3299-3304
[46]Lee JJ,Choi HJ,Yun M,et al.Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy[J].Angew Chem Int Ed Engl,2015,54(41):12020-12024
[47]Collins BC,Gunn RJ,Mckitrick TR,et al.Structural insights into VLR fine specificity for blood group carbohydrates[J].Structure,2017,25(11):1667-1678
[48]Saupe F,Reichel M,Huijbers EJ,et al.Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously[J].FASEB J,2017,31(3):1204-1214
[49]Kim HY,Lee JJ,Kim N,et al.Tracking protein-protein interaction and localization in living cells using a high-affinity molecular binder[J].Biochem Biophys Res Commun,2016,470(4):857-863
[50]Velásquez AC,Nomura K,Cooper MD,et al.Leucine-richrepeat-containing variable lymphocyte receptors as modules to target plant-expressed proteins[J].Plant Methods,2017,13:29
[51]Paatero A,Rosti K,Shkumatov AV,et al.Crystal structure of an engineered LRRTM2 synaptic adhesion molecule and a model for neurexin binding[J].Biochemistry,2016,55(6):914-926
[52]Kim HM,Park BS,Kim JI,et al.Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran[J].Cell,2007,130(5):906-917
[53]Lee JS,Kim J,Im SP,et al.Generation and characterization of hagfish variable lymphocyte receptor B against glycoprotein of viral hemorrhagic septicemia virus(VHSV)[J].Mol Immunol,2018,99:30-38
[54]Herrin BR,Alder MN,Roux KH,et al.Structure and specificity of lamprey monoclonal antibodies[J].Proc Natl Acad Sci USA,2008,105(6):2040-2045