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The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes.

Publication ,  Journal Article
Alam, SM; McAdams, M; Boren, D; Rak, M; Scearce, RM; Gao, F; Camacho, ZT; Gewirth, D; Kelsoe, G; Chen, P; Haynes, BF
Published in: J Immunol
April 1, 2007

Two neutralizing human mAbs, 2F5 and 4E10, that react with the HIV-1 envelope gp41 membrane proximal region are also polyspecific autoantibodies that bind to anionic phospholipids. To determine the autoantibody nature of these Abs, we have compared their reactivities with human anti-cardiolipin mAbs derived from a primary antiphospholipid syndrome patient. To define the role of lipid polyreactivity in binding of 2F5 and 4E10 mAbs to HIV-1 envelope membrane proximal epitopes, we determined the kinetics of binding of mAbs 2F5 and 4E10 to their nominal gp41 epitopes vs liposome-gp41 peptide conjugates. Both anti-HIV-1 mAbs 2F5 and 4E10 bound to cardiolipin with K(d) values similar to those of autoimmune anti-cardiolipin Abs, IS4 and IS6. Binding kinetics studies revealed that mAb 2F5 and 4E10 binding to their respective gp41 peptide-lipid conjugates could best be defined by a two-step (encounter-docking) conformational change model. In contrast, binding of 2F5 and 4E10 mAbs to linear peptide epitopes followed a simple Langmuir model. A mouse mAb, 13H11, that cross-blocks mAb 2F5 binding to the gp41 epitope did not cross-react with lipids nor did it neutralize HIV-1 viruses. Taken together, these data demonstrate the similarity of 2F5 and 4E10 mAbs to known anti-cardiolipin Abs and support the model that mAb 2F5 and 4E10 binding to HIV-1 involves both viral lipid membrane and gp41 membrane proximal epitopes.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

April 1, 2007

Volume

178

Issue

7

Start / End Page

4424 / 4435

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Mice
  • Liposomes
  • Lipids
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • Cardiolipins
 

Citation

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Alam, S. M., McAdams, M., Boren, D., Rak, M., Scearce, R. M., Gao, F., … Haynes, B. F. (2007). The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol, 178(7), 4424–4435. https://doi.org/10.4049/jimmunol.178.7.4424
Alam, S Munir, Mildred McAdams, David Boren, Michael Rak, Richard M. Scearce, Feng Gao, Zenaido T. Camacho, et al. “The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes.J Immunol 178, no. 7 (April 1, 2007): 4424–35. https://doi.org/10.4049/jimmunol.178.7.4424.
Alam SM, McAdams M, Boren D, Rak M, Scearce RM, Gao F, Camacho ZT, Gewirth D, Kelsoe G, Chen P, Haynes BF. The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol. 2007 Apr 1;178(7):4424–4435.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

April 1, 2007

Volume

178

Issue

7

Start / End Page

4424 / 4435

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Mice
  • Liposomes
  • Lipids
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • Cardiolipins