Antibody Complexes

  • Reetesh Raj Akhouri
  • Lars-Göran Öfverstedt
  • Gunnar Wilken
  • Ulf SkoglundEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 93)


Monoclonal based therapeutics have always been looked at as a futuristic natural way we could take care of pathogens and many diseases. However, in order to develop, establish and realize monoclonal based therapy we need to understand how the immune system contains or kill pathogens. Antibody complexes serve the means to decode this black box. We have discussed examples of antibody complexes both at biochemical and structural levels to understand and appreciate how discoveries in the field of antibody complexes have started to decoded mechanism of viral invasion and create potential vaccine targets against many pathogens. Antibody complexes have made advancement in our knowledge about the molecular interaction between antibody and antigen. It has also led to identification of potent protective monoclonal antibodies. Further use of selective combination of monoclonal antibodies have provided improved protection against deadly diseases. The administration of newly designed and improved immunogen has been used as potential vaccine. Therefore, antibody complexes are important tools to develop new vaccine targets and design an improved combination of monoclonal antibodies for passive immunization or protection with very little or no side effects.


Antibody Therapeutics Monoclonal antibody Vaccine Immunization Immunogen 


  1. Aboudola S, Kotloff KL, Kyne L, Sougioultzis S et al (2003) Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun. 71:1608–1610Google Scholar
  2. Abreu-Mota T, Hagen KR, Cooper K et al (2018) Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever. Nat Commun 9(1):4223. Scholar
  3. Akhouri RR, Goel S, Furusho H et al (2016) Architecture of human IgM in complex with P. falciparum erythrocyte membrane protein 1. Cell Rep. 14:723–736CrossRefPubMedGoogle Scholar
  4. Amon R, Reuven EM, Leviatan Ben-Arye S et al (2014) Carbohydr Res 389:115–22.
  5. Arunkumar GA, Ioannou A, Wohlbold TJ et al (2019) Broadly cross-reactive, non-neutralizing antibodies against the influenza B virus hemagglutinin demonstrate effector function dependent protection against lethal viral challenge in mice. J Virol pii: JVI.01696-18.
  6. Babcock GJ, Broering Teresa J et al (2006) Human monoclonal antibodies directed against Toxins A and B Prevent Clostridium difficile-induced mortality in hamsters. Infect Immun 74:6339–6347CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bailey JR, Flyak AI, Cohen VJ et al (2017) Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance. JCI Insight. 2:92872CrossRefPubMedGoogle Scholar
  8. Bartesaghi A, Merk A, Borgnia MJ et al (2013) Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy. Nat Struct Mol Biol 20:1352–1357CrossRefPubMedPubMedCentralGoogle Scholar
  9. Baruch DI, Pasloske B, Singh HB et al (1995) Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82:77–87Google Scholar
  10. Binley JM, Sanders RW, Master A et al (2002) Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins. J Virol 76:2606–2616CrossRefPubMedPubMedCentralGoogle Scholar
  11. Biswas AK, Hafiz A, Banerjee B et al (2007) Plasmodium falciparum uses gC1qR/HABP1/p32 as a receptor to bind to vascular endothelium and for platelet-mediated clumping. PLoS Pathog 3:1271–1280CrossRefPubMedGoogle Scholar
  12. Boes M (2000) Role of natural and immune IgM antibodies in immune responses. Mol Immunol 37:1141–1149CrossRefPubMedGoogle Scholar
  13. Bongini L, Fanelli D, Piazza F et al (2007) A dynamical study of antibody-antigen encounter reactions. Phys Biol 4:172–180CrossRefPubMedGoogle Scholar
  14. Bongini L, Fanelli D, Piazza F et al (2004) Freezing immunoglobulins to see them move. Proc Natl Acad Sci 101:6466–6471CrossRefPubMedGoogle Scholar
  15. Bongini L, Fanelli D, Piazza F et al (2005) Dynamics of antibodies from cryo-electron tomography. Biophys Chem 115:235–240CrossRefPubMedGoogle Scholar
  16. Borghesi L, Milcarek C (2006) From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion. Immunol Res 36:27–32CrossRefPubMedGoogle Scholar
  17. Broering TJ, Garrity KA, Boatright NK et al (2009) Identification and characterization of broadly neutralizing human monoclonal antibodiesdirected against the E2 envelope glycoprotein of hepatitis C virus. J Virol 83:12473–12482CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chan DC, Fass D, Berger JM et al (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89:263–273CrossRefPubMedGoogle Scholar
  19. Chehadeh W, Halim MA, Al-Nakib W (2009) Antibody mediated opsonization of red blood cells in parvovirus B19 infection. Virology 390:56–63. Scholar
  20. Chen Y, Park YB, Patel E et al (2009) IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells. J Immunol 182:6031–6043. Scholar
  21. Corti D, Misasi J, Mulangu S et al (2016) Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science 351:1339–1342CrossRefPubMedGoogle Scholar
  22. Coutinho A, Kazatchkine MD, Avrameas S (1995) Natural autoantibodies. Curr Opin Immunol 7:812–818CrossRefPubMedGoogle Scholar
  23. Crowley J, Chu C, Love GM et al (2010) Malaria in children. Lancet 375:1468–1481CrossRefGoogle Scholar
  24. Czajkowsky DM, Shao Z (2009) The human IgM pentamer is a mushroom-shaped molecule with a flexural bias. Proc Natl Acad Sci U S A. 106:14960–14965CrossRefPubMedPubMedCentralGoogle Scholar
  25. Doolan DL, Dobaño C, Baird JK (2009) Acquired immunity to malaria. Clin Microbiol Rev 22:13–36CrossRefPubMedPubMedCentralGoogle Scholar
  26. Dudley DD, Chaudhuri J, Bassing CH et al (2005) Mechanism and control of V(D)J recombination versus class switch recombination: similarities and differences. Adv Immunol 86:43–112CrossRefPubMedGoogle Scholar
  27. Feinstein A, Munn EA (1969) Conformation of the free and antigen-bound IgM antibody molecules. Nature 224:1307–1309CrossRefPubMedGoogle Scholar
  28. Fellah JS, Wiles MV, Charlemagne J et al (1992) Evolution of vertebrate IgM: complete amino acid sequence of the constant region of Ambystoma mexicanum mu chain deduced from cDNA sequence. Eur J Immunol 22:2595–2601CrossRefPubMedGoogle Scholar
  29. Flyak AI, Ilinykh PA, Murin CD et al (2015) Mechanism of human antibody mediated neutralization of Marburg virus. Cell 160:893–903. Scholar
  30. Franco S, Tural C, Nevot M et al (2014) Detection of a sexually transmitted hepatitis C virus protease inhibitor-resistance variant in a human immunodeficiency virus-infected homosexual man. Gastroenterology 147:599–601CrossRefPubMedGoogle Scholar
  31. Fuentes-Panana EM, Bannish G, Monroe JG (2004) Basal B-cell receptor signaling in B lymphocytes: mechanisms of regulation and role in positive selection, differentiation, and peripheral survival. Immunol Rev 197:26–40CrossRefPubMedGoogle Scholar
  32. Galanti M, Fanelli D, Piazza F (2016) Conformation-controlled binding kinetics of antibodies. Sci Rep 6:18976. Scholar
  33. Garces F, Lee JH, de Val N et al (2015) Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding Glycans. Immunity 43:1053–1063CrossRefPubMedPubMedCentralGoogle Scholar
  34. Gardner MJ, Hall N, Fung E et al (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511CrossRefPubMedGoogle Scholar
  35. Georgiev IS, Joyce MG, Yang Y et al (2015) Single-chain soluble BG505·SOSIP gp140 trimers as structural and antigenic mimics of mature closed HIV-1 Env. J Virol 89:5318–5329CrossRefPubMedPubMedCentralGoogle Scholar
  36. Germain RN (1994) MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 76:287–299CrossRefPubMedGoogle Scholar
  37. Gherardi E, Sandin S, Petoukhov MV et al (2006) Structural basis of hepatocyte growth factor/scatter factor and MET signalling. Proc Natl Acad Sci 103:4046–4051CrossRefPubMedGoogle Scholar
  38. Goel S, Pamkvist M, Moll K et al (2015). RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. Nat Med 21:314–317Google Scholar
  39. Gopal R, Jackson K, Tzarum N et al (2017) Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughputmutagenesis. PLoS Pathog 13:e1006735CrossRefPubMedPubMedCentralGoogle Scholar
  40. Gravitz L (2011) Introduction: a smouldering public-health crisis. Nature 474:2–4CrossRefGoogle Scholar
  41. Harris LJ, Larson SB, Hasel KW et al (1992) The three-dimensional structure of an intact monoclonal antibody for canine lymphoma. Nature 360:369–372CrossRefPubMedGoogle Scholar
  42. Harris LJ, Larson SB, Skaletsky E et al (1998) Comparison of the conformations of two intact monoclonal antibodies with hinges. Immunol Rev 163:35–43CrossRefPubMedGoogle Scholar
  43. Haury M, Sundblad A, Grandien A et al (1997) The repertoire of serum IgM in normal mice is largely independent of external antigenic contact. Eur J Immunol 27:1557–1563CrossRefPubMedGoogle Scholar
  44. Haynes BF, Moody MA, Verkoczy L et al (2005) Antibody polyspecificity and neutralization of HIV-1: a hypothesis. Hum Antibodies. 14:59–67CrossRefPubMedPubMedCentralGoogle Scholar
  45. Hippocrates (1959) On the nature of man. Harvard University Press, Cambridge, MAGoogle Scholar
  46. Holmberg SD, Spradling PR, Moorman AC et al (2013) Hepatitis C in the United States. N Engl J Med 368:1859–1861CrossRefPubMedPubMedCentralGoogle Scholar
  47. Hoofnagle JH (2002) Course and outcome of hepatitis C. Hepatology 36:21–29Google Scholar
  48. Janeway CA Jr, Travers P, Walport M et al (2001) Immunobiology: the immune system in health and disease, 5th edn. Garland Science, New YorkGoogle Scholar
  49. Jefferis R (2009) Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 8:226–234.
  50. Julien JP, Cupo A, Sok D et al (2013a) Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342:1477–1483CrossRefPubMedGoogle Scholar
  51. Julien JP, Lee JH, Cupo A et al (2013b) Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Natl Acad Sci U S A. 110:4351–4356CrossRefPubMedPubMedCentralGoogle Scholar
  52. Katzelnick LC, Montoya M, Gresh L et al (2016) Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. Proc Natl Acad Sci USA 113:728–733. Scholar
  53. Khayat R, Lee JH, Julien JP et al (2013) Structural characterization of cleaved, soluble HIV-1 envelope glycoprotein trimers. J Virol 87:9865–9872CrossRefPubMedPubMedCentralGoogle Scholar
  54. Kim MS, Chuenchor W, Chen X et al (2018) Cracking the DNA code for V(D)J recombination. Mol Cell 70:358–370. Scholar
  55. Kindred B, Shreffler DC (1972) H-2 dependence of co-operation between T and B cells in vivo. J Immunol 109:940–943PubMedGoogle Scholar
  56. Kisalu NK, Idris AH, Weidle C et al (2018) A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med 24:408–416CrossRefPubMedPubMedCentralGoogle Scholar
  57. Klasse PJ, Depetris RS, Pejchal R et al (2013) Influences on trimerization and aggregation of soluble, cleaved HIV-1 SOSIP envelope glycoprotein. J Virol 87:9873–9885CrossRefPubMedPubMedCentralGoogle Scholar
  58. Kong L, Giang E, Nieusma T et al (2012a) Structure of hepatitis C virus envelope glycoprotein E2 antigenic site 412 to 423 in complex with antibody AP33. J Virol 86:13085–13088CrossRefPubMedPubMedCentralGoogle Scholar
  59. Kong L, Giang E, Robbins JB et al (2012b) Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1. Proc Natl Acad Sci U S A. 109:9499–9504CrossRefPubMedPubMedCentralGoogle Scholar
  60. Kwong PD, Wyatt R, Robinson J et al (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648–659CrossRefPubMedPubMedCentralGoogle Scholar
  61. Lagging LM, Westin J, Svensson E et al (2002) Progression of fibrosis in untreated patients with hepatitis C virus infection. Liver 22:136–144CrossRefPubMedGoogle Scholar
  62. Law M, Maruyama T, Lewis J et al (2008) Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14:25–27CrossRefPubMedGoogle Scholar
  63. Lawrence MG, Woodfolk JA, Schuyler AJ et al (2017) Half-life of IgE in serum and skin: consequences for anti IgE therapy in patients with allergic disease. J Allergy Clin Immunol. 139:422–428CrossRefPubMedGoogle Scholar
  64. Lee JE, Fusco ML, Hessell AJ et al (2008) Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 454:177–182CrossRefPubMedPubMedCentralGoogle Scholar
  65. Lee JH, Ozorowski G, Ward AB (2016) Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 351:1043–1048CrossRefPubMedPubMedCentralGoogle Scholar
  66. Li Y, Pierce BG, Wang Q et al (2015) Structural basis for penetration of the glycan shield of hepatitis C virus E2 glycoprotein by a broadly neutralizing human antibody. J Biol Chem 290:10117–10125CrossRefPubMedPubMedCentralGoogle Scholar
  67. Liu J, Bartesaghi A, Borgnia MJ et al (2008) Molecular architecture of native HIV-1 gp120 trimers. Nature 455:109–113CrossRefPubMedPubMedCentralGoogle Scholar
  68. Lu X, Xiao H, Li S, Pang X, Song J et al (2019) Double lock of a human neutralizing and protective monoclonal antibody targeting the yellow fever virus envelope. Cell Rep. 26:438–446. Scholar
  69. Lyumkis D, Julien JP, de Val N et al (2013) Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342:1484–1490CrossRefPubMedPubMedCentralGoogle Scholar
  70. Maizels N (2005) Immunoglobulin gene diversification. Annu Rev Genet 39:23–46CrossRefPubMedGoogle Scholar
  71. Marquardt D, McCrone S, Center MS (1990) Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. Cancer Res 50:1426–1430PubMedGoogle Scholar
  72. Maruyama T, Rodriguez LL, Jahrling PB et al (1999) Ebola virus can be effectively neutralized by antibody produced in natural human infection. J Virol 73:6024–6030CrossRefPubMedPubMedCentralGoogle Scholar
  73. Meola A, Tarr AW, England P et al (2015) Structural flexibility of a conserved antigenic region in hepatitisvirus glycoprotein E2 recognized by broadly neutralizing antibodies. J Virol 89:2170–2181CrossRefPubMedGoogle Scholar
  74. Meunier JC, Russell RS, Goossens V et al (2008) Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1glycoprotein of hepatitis C virus. J Virol 82:966–973CrossRefPubMedGoogle Scholar
  75. Micoli F, Rondini S, Alfini R et al (2018) Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella. Proc Natl Acad Sci U S A. 115:10428–10433. Scholar
  76. Miller LH, Baruch DI, Marsh K et al (2002) The pathogenic basis of malaria. Nature 415:673–679CrossRefPubMedGoogle Scholar
  77. Mimura Y, Lund J, Church S et al (2001) Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile. J Immunol Methods 247:205–216CrossRefPubMedGoogle Scholar
  78. Murin CD, Fusco ML, Bornholdt ZA et al (2014) Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci U S A. 111:17182–17187CrossRefPubMedPubMedCentralGoogle Scholar
  79. Murphy KP, Travers P, Walport M (2008) Janeway’s immunobiology,7th edn. Garland Science, New YorkGoogle Scholar
  80. Noris M, Remuzzi G (2013) Overview of complement activation and regulation. Semin Nephrol 33(6):479–492. Scholar
  81. O’Meara WP, Mwangi TW, Williams et al (2008) Relationship between exposure, clinical malaria, and age in an area of changing transmission intensity. Am J Trop Med Hyg 79:185–191Google Scholar
  82. Ogden CA, Kowalewski R, Peng Y et al (2005) IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity 38:259–264CrossRefPubMedGoogle Scholar
  83. Olinger GG Jr, Pettitt J, Kim D et al (2012) Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc Natl Acad Sci U S A. 109:18030–18035CrossRefPubMedPubMedCentralGoogle Scholar
  84. Oswald WB, Geisbert TW, Davis KJ et al (2007) Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys. PLoS Pathog 3:e9CrossRefPubMedPubMedCentralGoogle Scholar
  85. Oyen D, Torres JL, Cottrell CA et al (2018) Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts. Sci Adv 4:eaau8529Google Scholar
  86. Oyen D, Torres JL, Wille-Reece U et al (2017) Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 114:E10438–E10445CrossRefPubMedPubMedCentralGoogle Scholar
  87. Pancera M, Zhou T, Druz A et al (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514:455–461CrossRefPubMedPubMedCentralGoogle Scholar
  88. Parren PW, Geisbert TW, Maruyama T et al (2002) Pre- and postexposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol 76:6408–6412CrossRefPubMedPubMedCentralGoogle Scholar
  89. Paterson Y, Englander SW, Roder H (1990) An antibody binding site on cytochrome c defined by hydrogen exchange and two-dimensional NMR. Science 249:755–759CrossRefPubMedPubMedCentralGoogle Scholar
  90. Pauthner MG, Nkolola JP, Havenar-Daughton C et al (2018) Vaccine-induced protection from homologous Tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers. Immunity 50:241–252. Scholar
  91. Perkins SJ, Nealis AS, Sutton BJ et al (1991) Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. J Mol Biol 221:1345–1366CrossRefPubMedGoogle Scholar
  92. Petrušić V, Živković I, Stojanović M et al (2011) Hexameric immunoglobulin M in humans: desired or unwanted? Med Hypotheses 77:959–961CrossRefPubMedGoogle Scholar
  93. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera? A visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612Google Scholar
  94. Piazza F, De Los Rios P, Fanelli D et al (2005) Anti-cooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter. Eur Biophys J 34:899–911CrossRefPubMedGoogle Scholar
  95. Pier GB, Lyczak JB, Wetzler LM (2004) Immunology, infection, and immunity. ASM Press. ISBN 1-55581-246-5Google Scholar
  96. Pierce BG, Keck ZY, Lau P et al (2016) Global mapping of antibody recognition of the hepatitis C virus E2 glycoprotein: implications for vaccine design. Proc Natl Acad Sci U S A. 113:E6946–E6954CrossRefPubMedPubMedCentralGoogle Scholar
  97. Pisetsky DS (1997) Specificity and immunochemical properties of antibodies to bacterial DNA. Methods 11:55–61CrossRefPubMedGoogle Scholar
  98. Pisetsky DS (1998) Antibody responses to DNA in normal immunity and aberrant immunity. Clin Diagn Lab Immunol 5:1–6CrossRefPubMedPubMedCentralGoogle Scholar
  99. Potter JA, Owsianka AM, Jeffery N et al (2012) Toward a hepatitis C virus vaccine: the structural basis of hepatitis C virus neutralization by AP33, a broadly neutralizing antibody. J Virol 86:12923–12932CrossRefPubMedPubMedCentralGoogle Scholar
  100. PyMOL software.
  101. Quartier P, Potter PK, Ehrenstein MR et al (2005) Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol 35:252–260CrossRefPubMedGoogle Scholar
  102. Randall TD, Brewer JW, Corley RB (1992) Direct evidence that J chain regulates the polymeric structure of IgM in antibody-secreting B cells. J Biol Chem 267:18002–18007PubMedGoogle Scholar
  103. Randall TD, King LB, Corley RB (1990) The biological effects of IgM hexamer formation. Eur J Immunol 20:1971–1979CrossRefPubMedGoogle Scholar
  104. Rayner LE, Kadkhodayi-Kholghi N, Heenan et al (2013) The solution structure of rabbit IgG accounts for its interactions with the Fc receptor and complement C1q and its conformational stability. J Mol Biol 425:506–523Google Scholar
  105. Robbiani DF, Bozzacco L, Keeffe JR et al (2017) Recurrent potent human neutralizing antibodies to Zika Virus in Brazil and Mexico. Cell 169:597–609.e11.
  106. Roberts DJ, Pain A, Kai O et al (2000) Autoagglutination of malaria-infected red blood cells and malaria severity. Lancet 355:1427–1428CrossRefPubMedGoogle Scholar
  107. Roche PA, Cresswell P (1991) Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules. Proc Natl Acad Sci U S A. 88:3150–3154CrossRefPubMedPubMedCentralGoogle Scholar
  108. Rosenthal AS, Shevach EM (1973) Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med 138:1194–1212CrossRefPubMedPubMedCentralGoogle Scholar
  109. Rudkin FM, Raziunaite I, Workman H et al (2018) Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nat Commun. 9:5288. Scholar
  110. Saito F, Hirayasu K, Satoh T et al (2017) Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors. Nature 552:101–105CrossRefPubMedPubMedCentralGoogle Scholar
  111. Sanders RW, de Jong EC, Baldwin CE et al (2002) Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells. J Virol 76:7812–7821CrossRefPubMedPubMedCentralGoogle Scholar
  112. Sanders RW, Moore JP (2017) Native-like Env trimers as a platform for HIV-1 vaccine design. Immunol Rev 275:161–182. Scholar
  113. Sanders RW, Schiffner L, Master et al (2000) Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits. J Virol 74:5091–100Google Scholar
  114. Sandin S, Öfverstedt LG, Wikström et al (2004). Structure and flexibility of individual immunoglobulin G molecules in solution. Structure 12: 409–415Google Scholar
  115. Saphire EO, Parren PW, Pantophlet R et al (2001) Crystal structure of a neutralizing human IgG against HIV-1: template for vaccine design. Science 293:1155–1159CrossRefPubMedGoogle Scholar
  116. Scapin G, Yang X, Prosise WW et al (2015) Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat Struct Mol Biol 22:953–958CrossRefPubMedGoogle Scholar
  117. Scherf A, Lopez-Rubio JJ, Riviere L (2008) Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol 62:445–470CrossRefPubMedGoogle Scholar
  118. Schlosstein L, Terasaki PI, Bluestone R et al (1973) High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med 288:704–706CrossRefPubMedGoogle Scholar
  119. Schroeder HW Jr, Cavacini L (2010) Structure and function of immunoglobulins. J Allergy Clin Immunol. 125:41–52. Scholar
  120. Sharma SK, de Val N, Bale S et al (2015) Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 11:539–550CrossRefPubMedPubMedCentralGoogle Scholar
  121. Smith DB, Bukh J, Kuiken C et al (2014) Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 59:318–327CrossRefPubMedGoogle Scholar
  122. Su XZ, Heatwole VM, Wertheimer SP et al (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82:89–100CrossRefPubMedGoogle Scholar
  123. Sun Z, Almogren A, Furtado PB et al (2005) Semi-extended solution structure of human myeloma immunoglobulin D determined by constrained X-ray scattering. J Mol Biol 353:155–173CrossRefPubMedGoogle Scholar
  124. Tan J, Piccoli L, Lanzavecchia A (2018) The Antibody Response to Plasmodium falciparum: cues for vaccine design and the discovery of receptor-based antibodies. Annu Rev Immunol.
  125. Tan J, Pieper K, Piccoli L et al (2016) A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature 529:105–109CrossRefPubMedGoogle Scholar
  126. Tan K, Liu J, Wang J et al (1997) Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci U S A. 94:12303–12308CrossRefPubMedPubMedCentralGoogle Scholar
  127. Tran EE, Borgnia MJ, Kuybeda O et al (2012) Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog 8:e1002797CrossRefPubMedPubMedCentralGoogle Scholar
  128. Vilhena JG, Dumitru AC, Herruzo ET et al (2016) Adsorption orientations and immunological recognition of antibodies on graphene. Nanoscale 8:13463–13475CrossRefPubMedGoogle Scholar
  129. Vollmers HP, Brandlein S (2006) Natural IgM antibodies: the orphaned molecules in immune surveillance. Adv Drug Deliv Rev 58:755–765CrossRefPubMedGoogle Scholar
  130. Wahlgren M, Goel S, Akhouri RR (2017) Variant surface antigens of Plasmodium falciparum and their roles in severe malaria. Nat Rev Microbiolgy. 15-479-491Google Scholar
  131. Wec AZ, Bornholdt ZA, He S, Herbert AS et al (2019) Development of a human antibody cocktail that deploys multiple functions to confer pan-ebolavirus protection. Cell Host Microbe 25(39–48):e5. Scholar
  132. Weissenhorn W, Dessen A, Harrison SC et al (1997) Atomic structure of the ectodomain from HIV-1 gp41. Nature 387:426–430CrossRefPubMedGoogle Scholar
  133. Wilson JA, Hevey M, Bakken R et al (2000) Epitopes involved in antibody-mediated protection from Ebola virus. Science 287:1664–1666CrossRefPubMedGoogle Scholar
  134. Wong-Baeza C, Reséndiz-Mora A, Donis-Maturano L et al (2016) Anti-lipid IgG antibodies are produced via Germinal Centers in a murine model resembling human lupus. Front Immunol 7:396CrossRefPubMedPubMedCentralGoogle Scholar
  135. Woof J, Burton D (2004) Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 4:89–99CrossRefPubMedGoogle Scholar
  136. Zanetti G, Briggs JA, Grünewald K et al (2006) Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog 2:e83CrossRefPubMedPubMedCentralGoogle Scholar
  137. Zeitlin L, Pettitt J, Scully C et al (2011) Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proc Natl Acad Sci U S A. 108:20690–20694CrossRefPubMedPubMedCentralGoogle Scholar
  138. Zhang J, Liu D, Li G et al (2017) Antibody mediated neutralization of soluble MIC significantly enhances CTLA4 blockade therapy. Sci Adv 3(5):e1602133.
  139. Zhu P, Chertova E, Bess J Jr et al (2003) Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci U S A. 100:15812–15817CrossRefPubMedPubMedCentralGoogle Scholar
  140. Zhu P, Liu J, Bess J Jr et al (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441:847–852CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Reetesh Raj Akhouri
    • 1
  • Lars-Göran Öfverstedt
    • 1
  • Gunnar Wilken
    • 1
  • Ulf Skoglund
    • 1
    Email author
  1. 1.Okinawa Institute of Science and Technology Graduate UniversityOkinawaJapan

Personalised recommendations