Immunology: Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies

Science

Volumn 308, Issue 5730, 2005, Pages 1906-1908

  Haynes, Barton F ^a   Fleming, Judith ^a   St Clair, E William ^a   Katinger, Herman ^b   Stiegler, Gabriela ^b   Kunert, Renate ^b   Robinson, James ^c   Scearce, Richard M ^a   Plonk, Kelly ^a   Staats, Herman F ^a   Ortel, Thomas L ^a   Liao, Hua Xin ^a   Alam, S Munir ^a  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^c TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MEMBRANES; IMMUNOLOGY; PHOSPHOLIPIDS; VACCINES; VIRUSES;

AUTOREACTIVITY; CARDIOLIPIN; HUMAN IMMUNODEFICIENCY VIRUS-1 (HIV-1); MONOCLONAL ANTIBODIES (MABS);

ANTIBODIES;

AUTOANTIBODY; AUTOANTIGEN; BETA2 GLYCOPROTEIN 1; CARDIOLIPIN; CD4 ANTIGEN; CHEMOKINE RECEPTOR; DOUBLE STRANDED DNA; EPITOPE; GLUTAMYLLEUCYLASPARTYLLYSYLTRYPTOPHYLALANINE; GLYCOPROTEIN GP 140; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G1B12; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 2F5; MONOCLONAL ANTIBODY 4E10; NEUTRALIZING ANTIBODY; PEPTIDE DERIVATIVE; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLSERINE; PHOSPHOLIPID; POLYCLONAL ANTIBODY; PROTHROMBIN; RO ANTIBODY; SPHINGOMYELIN; UNCLASSIFIED DRUG; VIRUS ANTIGEN; VIRUS ENVELOPE PROTEIN;

MEDICINE;

AMINO ACID SEQUENCE; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY SPECIFICITY; ANTIGEN ANTIBODY REACTION; ARTICLE; AUTOIMMUNE DISEASE; B LYMPHOCYTE; BINDING AFFINITY; BINDING SITE; DRUG SYNTHESIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROPHOBICITY; IC 50; IMMUNIZATION; IMMUNOASSAY; IMMUNOLOGICAL TOLERANCE; IMMUNOREACTIVITY; IMMUNOREGULATION; MOLECULAR MIMICRY; NONHUMAN; PRIORITY JOURNAL; SYSTEMIC LUPUS ERYTHEMATOSUS; VIRUS ENVELOPE; ANIMAL; CHEMISTRY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MOUSE; SERODIAGNOSIS; TUMOR CELL LINE;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

AIDS VACCINES; ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODY SPECIFICITY; AUTOANTIBODIES; AUTOANTIGENS; AUTOIMMUNE DISEASES; CARDIOLIPINS; CELL LINE, TUMOR; EPITOPES; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; HUMANS; MICE; MOLECULAR MIMICRY; NEUTRALIZATION TESTS;

EID: 21344434534     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1111781     Document Type: Article

References (35)

1. D. R. Burton et al., Nat. Immunol. 5, 233 (2004).
2. O. Stiegler, H. Katinger, J. Antimicrobiol. Chemother. 51, 757 (2003).
3. G. Ofek et al., J. Virol. 19, 10724 (2004).
4. R. M. F. Cardoso et al., Immunity 22, 163 (2005).
5. D. Opalka et al., J. Immunol. Methods 287, 49 (2004).
6. 50 < 0.1 μg/ml). Using this extremely sensitive and specific assay, they were unable to detect either 4E10- or 2F5-like neutralizing antibodies in any one of 175 HIV-1-infected individuals representing the same 10 HIV-1 subtypes or circulating recombinant forms.
7. C. B. McCaughey et al., Biochemistry 42, 3214 (2003).
8. Haynes and colleagues (32) have immunized guinea pigs and rabbits with constrained HIV-1 Env immunogens that have 2FS and 4E10 epitopes stably expressed and have found that neither animal model responded to immunization with HIV-1 Envs with broadly reactive neutralizing antibodies or with antibodies against the 2F5 or 4E10 epitopes.
9. E. Meffre et al., J. Clin. Invest. 108, 879 (2001).
10. C. Petrovas et al., J. Autoimmun. 13, 347 (1999).
11. D. A. Calarese et al., Science 300, 2065 (2003).
12. J. A. Kessler et al., AIDS Res. Hum. Retroviruses 13, 575 (1997).
13. C. N. Scanlan et al., Adv. Exp. Med. Biol. 535, 205 (2003).
14. Materials and methods are available as supporting material on Science Online.
15. M. Fenger et al., Clin. Chem. 50, 2141 (2004).
16. E. L. Radway-Bright, C. T. Ravirajam, D. A. Isenberg, Rheumatology 39, 427 (2000).
17. J. Delgado-Alves et al., Arthritis Rheum. 46, 2686 (2002).
18. E. M. Bevers, M. Calli, T. Barbui, P. Comfurius, R. F. Zwaal, Thromb. Haemostasis 66, 629 (1991).
19. J. Guerin et al., Br. J. Haematol. 102, 896 (1998).
20. M. Zhu et al., Br. J. Haematol. 105, 102 (1999).
21. R. Kunert et al., AIDS 16, 667 (2002).
22. C. Barbato et al., J. Mol. Biol. 330, 1101 (2003).
23. L. Weiss et al., Clin. Immunol. Immunopathol. 77, 69 (1995).
24. N. Abuaf et al., Thromb. Haemostasis 77, 856 (1997).
25. S. Loizou et al., Ann. Rheum. Dis. 62, 1106 (2003).
26. R. A. Fox, D. A. Isenberg, Arthritic Rheum. 40, 1168 (1997).
27. R. Palacios, J. Santos, Int. J. STD AIDS 15, 277 (2004).
28. A. Douvas, Y. Takehana, C. Ehresmann, T. Chernyovskiy, E. S. Daar, AIDS Res. Human Retrovirol. 12, 1509 (1996).
29. J. P. Bouvet, G. Dighiero, Infect. Immun. 66, 1 (1998).
30. F. Martin, A. M. Oliver, J. F. Kearney, Immunity 14, 617 (2001).
31. G. Shaw et al., personal communication.
32. B. F. Haynes et al., unpublished observations.
33. B. F. Haynes et al., data not shown.
34. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
35. Supported by the Duke Center for Translational Research NIH grant AI51445 and by NIH grant PO-1 AI52816. The authors thank D. Howell for fluorescent microscopy; D. Burton and the AIDS Reagent Repository for mAbs IgG1b12 and 447-52D, respectively; G. Kelsoe and T, Kepler for insightful discussions; and D. Lewis and K. Klemp for coagulation assays.