Immunologic basis for long HCDR3s in broadly neutralizing antibodies against HIV-1

Frontiers in Immunology

Volumn 5, Issue JUN, 2014, Pages

  Yu, Lei ^a   Guan, Yongjun ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Broadly neutralizing antibodies; HIV 1; Immunologic mechanism; Long HCDR3; Vaccines; VH replacement

Indexed keywords

EID: 84905672117     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00250     Document Type: Review

References (95)

1. Baba TW, Liska V, Hofmann-Lehmann R, Vlasak J, Xu W, Ayehunie S, et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med (2000) 6:200-6. doi: 10.1038/72309
2. Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, et al. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med (2014) 20:296-300. doi:10.1038/nm.3471
3. Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, Liu J, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature (2013) 503:224-8. doi:10.1038/nature12744
4. Hessell AJ, Poignard P, Hunter M, Hangartner L, Tehrani DM, Bleeker WK, et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med (2009) 15:951-4. doi:10.1038/nm.1974
5. Horwitz JA, Halper-Stromberg A, Mouquet H, Gitlin AD, Tretiakova A, Eisenreich TR, et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc Natl Acad Sci U S A (2013) 110:16538-43. doi:10.1073/pnas.1315295110
6. Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature (2012) 492:118-22. doi:10.1038/nature11604
7. Mascola JR, Lewis MG, Stiegler G, Harris D, VanCott TC, Hayes D, et al. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol (1999) 73:4009-18.
8. Moldt B, Rakasz EG, Schultz N, Chan-Hui PY, Swiderek K, Weisgrau KL, et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci U S A (2012) 109:18921-5. doi:10.1073/pnas.1214785109
9. Shibata R, Igarashi T, Haigwood N, Buckler-White A, Ogert R, Ross W, et al. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nat Med (1999) 5:204-10. doi:10.1038/5568
10. Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature (2013) 503:277-80. doi:10.1038/nature12746
11. Veazey RS, Shattock RJ, Pope M, Kirijan JC, Jones J, Hu Q, et al. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nat Med (2003) 9:343-6. doi:10.1038/nm833
12. Burton DR, Poignard P, Stanfield RL, Wilson IA. Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science (2012) 337:183-6. doi:10.1126/science.1225416
13. Haynes BF, McElrath MJ. Progress in HIV-1 vaccine development. Curr Opin HIV AIDS (2013) 8:326-32. doi:10.1097/COH.0b013e328361d178
14. Koff WC. HIV vaccine development: challenges and opportunities towards solving the HIV vaccine-neutralizing antibody problem. Vaccine (2011) 30(29):4310-5. doi:10.1016/j.vaccine.2011.11.014
15. Kwong PD, Mascola JR, Nabel GJ. The changing face of HIV vaccine research. J Int AIDS Soc (2012) 15:17407. doi:10.7448/IAS.15.2.17407
16. Kwong PD, Mascola JR, Nabel GJ. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol (2013) 13:693-701. doi:10.1038/nri3516
17. Mouquet H, Nussenzweig MC. HIV: roadmaps to a vaccine. Nature (2013) 496:441-2. doi:10.1038/nature12091
18. Sattentau QJ, McMichael AJ. New templates for HIV-1 antibody-based vaccine design. F1000 Biol Rep (2010) 2:60. doi:10.3410/B2-60
19. Stamatatos L. HIV vaccine design: the neutralizing antibody conundrum. Curr Opin Immunol (2012) 24:316-23. doi:10.1016/j.coi.2012.04.006
20. West AP Jr, Scharf L, Scheid JF, Klein F, Bjorkman PJ, Nussenzweig MC. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell (2014) 156:633-48. doi:10.1016/j.cell.2014.01.052
21. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, et al. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol (2011) 85:9998-10009. doi:10.1128/JVI.05045-11
22. Corti D, Langedijk JP, Hinz A, Seaman MS, Vanzetta F, Fernandez-Rodriguez BM, et al. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS One (2010) 5:e8805. doi:10.1371/journal.pone.0008805
23. Georgiev IS, Doria-Rose NA, Zhou T, Kwon YD, Staupe RP, Moquin S, et al. Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science (2013) 340:751-6. doi:10.1126/science.1233989
24. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature (2012) 491:406-12. doi:10.1038/nature11544
25. Li Y, O'Dell S, Wilson R, Wu X, Schmidt SD, Hogerkorp CM, et al. HIV-1 neutralizing antibodies display dual recognition of the primary and coreceptor binding sites and preferential binding to fully cleaved envelope glycoproteins. J Virol (2012) 86:11231-41. doi:10.1128/JVI.01543-12
26. Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature (2013) 496:469-76. doi:10.1038/nature12053
27. Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature (2009) 458:636-40. doi:10.1038/nature07930
28. 4 binding. Science (2011) 333:1633-7. doi:10.1126/science.1207227
29. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature (2011) 477:466-70. doi:10.1038/nature10373
30. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science (2009) 326:285-9. doi:10.1126/science.1178746
31. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science (2010) 329:856-61. doi:10.1126/science.1187659
32. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science (2011) 333:1593-602. doi:10.1126/science.1207532
33. Zhou T, Zhu J, Wu X, Moquin S, Zhang B, Acharya P, et al. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity (2013) 39:245-58. doi:10.1016/j.immuni.2013.04.012
34. Chang TW. Selecting low frequency antigen-specific single B lymphocytes. In: Ueberheide B, editor. United States Patent Number 5326696. Houston, TX: Tanox Biosystems, Inc. (1994).
35. Scheid JF, Mouquet H, Feldhahn N, Walker BD, Pereyra F, Cutrell E, et al. A method for identification of HIV gp140 binding memory B cells in human blood. J Immunol Methods (2009) 343:65-7. doi:10.1016/j.jim.2008.11.012
36. Simek MD, Rida W, Priddy FH, Pung P, Carrow E, Laufer DS, et al. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol (2009) 83:7337-48. doi:10.1128/JVI.00110-09
37. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science (2003) 301:1374-7. doi:10.1126/science.1086907
38. Doores KJ, Fulton Z, Huber M, Wilson IA, Burton DR. Antibody 2G12 recognizes di-mannose equivalently in domain- and nondomain-exchanged forms but only binds the HIV-1 glycan shield if domain exchanged. J Virol (2010) 84:10690-9. doi:10.1128/JVI.01110-10
39. Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science (2013) 342:1477-83. doi:10.1126/science.1245625
40. Lyumkis D, Julien JP, de Val N, Cupo A, Potter CS, Klasse PJ, et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science (2013) 342:1484-90. doi:10.1126/science.1245627
41. Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang SH, et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature (2007) 445:732-7. doi:10.1038/nature05580
42. Kong L, Lee JH, Doores KJ, Murin CD, Julien JP, McBride R, et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol (2013) 20(7):796-803. doi:10.1038/nsmb.2594
43. Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A (2012) 109:E3268-77. doi:10.1073/pnas.1217207109
44. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang PS, Wang SK, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science (2011) 334:1097-103. doi:10.1126/science.1213256
45. Blattner C, Lee JH, Sliepen K, Derking R, Falkowska E, de la Pena AT, et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity (2014) 40:669-80. doi:10.1016/j.immuni.2014.04.008
46. Falkowska E, Le KM, Ramos A, Doores KJ, Lee JH, Blattner C, et al. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity (2014) 40:657-68. doi:10.1016/j.immuni.2014.04.009
47. Scharf L, Scheid JF, Lee JH, West AP Jr, Chen C, Gao H, et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep (2014) 7(3):785-95. doi:10.1016/j.celrep.2014.04.001
48. Buchacher A, Predl R, Strutzenberger K, Steinfellner W, Trkola A, Purtscher M, et al. Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retroviruses (1994) 10:359-69. doi:10.1089/aid.1994.10.359
49. Zhu Z, Qin HR, Chen W, Zhao Q, Shen X, Schutte R, et al. Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies. J Virol (2011) 85:11401-8. doi:10.1128/JVI.05312-11
50. Mascola JR, Haynes BF. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev (2013) 254:225-44. doi:10.1111/imr.12075
51. Lefranc MP, Giudicelli V, Ginestoux C, Jabado-Michaloud J, Folch G, Bellahcene F, et al. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res (2009) 37:D1006-12. doi:10.1093/nar/gkn838
52. Liao H, Guo JT, Lange MD, Fan R, Zemlin M, Su K, et al. Contribution of V(H) replacement products to the generation of anti-HIV antibodies. Clin Immunol (2013) 146:46-55. doi:10.1016/j.clim.2012.11.003
53. Kwong PD, Mascola JR. Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity (2012) 37:412-25. doi:10.1016/j.immuni.2012.08.012
54. Tiller T, Tsuiji M, Yurasov S, Velinzon K, Nussenzweig MC, Wardemann H. Autoreactivity in human IgG+ memory B cells. Immunity (2007) 26:205-13. doi:10.1016/j.immuni.2007.01.009
55. Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med (2011) 208:181-93. doi:10.1084/jem.20101352
56. Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, et al. Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. Nat Med (2012) 18:1688-92. doi:10.1038/nm.2985
57. Wibmer CK, Bhiman JN, Gray ES, Tumba N, Abdool Karim SS, Williamson C, et al. Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes. PLoS Pathog (2013) 9:e1003738. doi:10.1371/journal.ppat.1003738
58. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol (2012) 30:429-57. doi:10.1146/annurev-immunol-020711-075032
59. Haynes BF, Fleming J, St Clair EW, Katinger H, Stiegler G, Kunert R, et al. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science (2005) 308:1906-8. doi:10.1126/science.1111781
60. Verkoczy L, Diaz M. Autoreactivity in HIV-1 broadly neutralizing antibodies: implications for their function and induction by vaccination. Curr Opin HIV AIDS (2014) 9:224-34. doi:10.1097/COH.0000000000000049
61. Haynes BF, Kelsoe G, Harrison SC, Kepler TB. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat Biotechnol (2012) 30:423-33. doi:10.1038/nbt.2197
62. Mouquet H, Nussenzweig MC. Polyreactive antibodies in adaptive immune responses to viruses. Cell Mol Life Sci (2012) 69:1435-45. doi:10.1007/s00018-011-0872-6
63. Ota T, Doyle-Cooper C, Cooper AB, Doores KJ, Aoki-Ota M, Le K, et al. B cells from knock-in mice expressing broadly neutralizing HIV antibody b12 carry an innocuous B cell receptor responsive to HIV vaccine candidates. J Immunol (2013) 191:3179-85. doi:10.4049/jimmunol.1301283
64. Wu TT, Johnson G, Kabat EA. Length distribution of CDRH3 in antibodies. Proteins (1993) 16:1-7. doi:10.1002/prot.340160102
65. Zemlin M, Klinger M, Link J, Zemlin C, Bauer K, Engler JA, et al. Expressed murine and human CDR-H3 intervals of equal length exhibit distinct repertoires that differ in their amino acid composition and predicted range of structures. J Mol Biol (2003) 334:733-49. doi:10.1016/j.jmb.2003.10.007
66. Ivanov II, Schelonka RL, Zhuang Y, Gartland GL, Zemlin M, Schroeder HW Jr. Development of the expressed Ig CDR-H3 repertoire is marked by focusing of constraints in length, amino acid use, and charge that are first established in early B cell progenitors. J Immunol (2005) 174:7773-80. doi:10.4049/jimmunol.174.12.7773
67. Arnaout R, Lee W, Cahill P, Honan T, Sparrow T, Weiand M, et al. High-resolution description of antibody heavy-chain repertoires in humans. PLoS One (2011) 6:e22365. doi:10.1371/journal.pone.0022365
68. Briney BS, Willis JR, Crowe JE Jr. Human peripheral blood antibodies with long HCDR3s are established primarily at original recombination using a limited subset of germline genes. PLoS One (2012) 7:e36750. doi:10.1371/journal.pone.0036750
69. Ohno S, Mori N, Matsunaga T. Antigen-binding specificities of antibodies are primarily determined by seven residues of VH. Proc Natl Acad Sci U S A (1985) 82:2945-9. doi:10.1073/pnas.82.9.2945
70. Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell (2002) 109(Suppl):S45-55. doi:10.1016/S0092-8674(02)00675-X
71. Tonegawa S. Somatic generation of antibody diversity. Nature (1983) 302:575-81. doi:10.1038/302575a0
72. Briney BS, Crowe JE Jr. Secondary mechanisms of diversification in the human antibody repertoire. Front Immunol (2013) 4:42. doi:10.3389/fimmu.2013.00042
73. Chen C, Nagy Z, Prak EL, Weigert M. Immunoglobulin heavy chain gene replacement: a mechanism of receptor editing. Immunity (1995) 3:747-55. doi:10.1016/1074-7613(95)90064-0
74. Wilson PC, Wilson K, Liu YJ, Banchereau J, Pascual V, Capra JD. Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes. J Exp Med (2000) 191:1881-94. doi:10.1084/jem.191.11.1881
75. Zhang Z, Burrows PD, Cooper MD. The molecular basis and biological significance of VH replacement. Immunol Rev (2004) 197:231-42. doi:10.1111/j.0105-2896.2004.0107.x
76. Reason DC, Zhou J. Codon insertion and deletion functions as a somatic diversification mechanism in human antibody repertoires. Biol Direct (2006) 1:24. doi:10.1186/1745-6150-1-24
77. Wilson PC, de Bouteiller O, Liu YJ, Potter K, Banchereau J, Capra JD, et al. Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes. J Exp Med (1998) 187:59-70. doi:10.1084/jem.187.1.59
78. Briney BS, Willis JR, Crowe JE Jr. Location and length distribution of somatic hypermutation-associated DNA insertions and deletions reveals regions of antibody structural plasticity. Genes Immun (2012) 13:523-9. doi:10.1038/gene.2012.28
79. Briney BS, Willis JR, Hicar MD, Thomas JW II, Crowe JE Jr. Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire. Immunology (2012) 137:56-64. doi:10.1111/j.1365-2567.2012.03605.x
80. Klonowski KD, Primiano LL, Monestier M. Atypical VH-D-JH rearrangements in newborn autoimmune MRL mice. J Immunol (1999) 162:1566-72.
81. 3 regions. J Immunol (1991) 147:1720-9.
82. Watson LC, Moffatt-Blue CS, McDonald RZ, Kompfner E, Ait-Azzouzene D, Nemazee D, et al. Paucity of V-D-D-J rearrangements and VH replacement events in lupus prone and nonautoimmune TdT-/- and TdT+/+ mice. J Immunol (2006) 177:1120-8. doi:10.4049/jimmunol.177.2.1120
83. Darlow JM, Stott DI. V(H) replacement in rearranged immunoglobulin genes. Immunology (2005) 114:155-65. doi:10.1111/j.1365-2567.2004.02084.x
84. Zhang Z, Zemlin M, Wang YH, Munfus D, Huye LE, Findley HW, et al. Contribution of VH gene replacement to the primary B cell repertoire. Immunity (2003) 19:21-31. doi:10.1016/S1074-7613(03)00170-5
85. Koralov SB, Novobrantseva TI, Konigsmann J, Ehlich A, Rajewsky K. Antibody repertoires generated by VH replacement and direct VH to JH joining. Immunity (2006) 25:43-53. doi:10.1016/j.immuni.2006.04.016
86. Nemazee D. Receptor editing in lymphocyte development and central tolerance. Nat Rev Immunol (2006) 6:728-40. doi:10.1038/nri1939
87. Yunk L, Meng W, Cohen PL, Eisenberg RA, Luning Prak ET. Antibodies in a heavy chain knock-in mouse exhibit characteristics of early heavy chain rearrangement. J Immunol (2009) 183:452-61. doi:10.4049/jimmunol.0804060
88. Zhang Z. VH replacement in mice and humans. Trends Immunol (2007) 28:132-7. doi:10.1016/j.it.2007.01.003
89. Huang L, Lange MD, Zhang Z. VH replacement footprint analyzer-I, a java-based computer program for analyses of immunoglobulin heavy chain genes and potential VH replacement products in human and mouse. Front Immunol (2014) 5:40. doi:10.3389/fimmu.2014.00040
90. Meng W, Jayaraman S, Zhang B, Schwartz GW, Daber RD, Hershberg U, et al. Trials and tribulations with VH replacement. Front Immunol (2014) 5:10. doi:10.3389/fimmu.2014.00010
91. Liu J, Lange MD, Hong SY, Xie W, Xu K, Huang L, et al. Regulation of VH replacement by B cell receptor-mediated signaling in human immature B cells. J Immunol (2013) 190:5559-66. doi:10.4049/jimmunol.1102503
92. Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature (2014) 509:55-62. doi:10.1038/nature13036
93. McGuire AT, Glenn JA, Lippy A, Stamatatos L. Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D. J Virol (2014) 88:2645-57. doi:10.1128/JVI.03228-13
94. Jardine J, Julien JP, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science (2013) 340:711-6. doi:10.1126/science.1234150
95. Guan Y, Liu T, Sajadi MM, Yu L, Huang W, Seaman M, et al. A common transitional Env conformation revealed by a new broadly neutralizing antibody as a novel HIV-1 vaccine target. AIDS Vaccine 2013. Barcelona: (2013). 13.56 p.