Lipid binding properties of 4E10, 2175, and WR304 monoclonal antibodies that neutralize HIV-1

被引:60
作者
Matyas, Gary R. [1 ]
Beck, Zoltan [1 ,2 ]
Karasawas, Nicos [1 ]
Alving, Carl R. [1 ]
机构
[1] Walter Reed Army Med Ctr, US Mil HIV Res Program, Div Retrovirol, Dept Adjuvant & Antigen Res, Rockville, MD 20850 USA
[2] Henry M Jackson Fdn Adv Mil Med, Rockville, MD 20850 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2009年 / 1788卷 / 03期
关键词
HIV-1; Antibody; Phospholipid; Cholesterol; Glycolipid; Lipid A; IMMUNODEFICIENCY-VIRUS TYPE-1; 2F5; LIPOSOMES; PROTEIN; EPITOPE; GP41; AUTOREACTIVITY; SPECIFICITIES; RECOGNIZES; REACTIVITY;
D O I
10.1016/j.bbamem.2008.11.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two human mAbs (25 and 4E10), originally derived from HIV-1-infected patients, are important, but rare, mAbs that exhibit broad cross-clade neutralizing activities against HIV-1. In addition to peptide sequences on the gp41 envelope protein, both antibodies reportedly also bound specifically to several phospholipid antigens. However, the phospholipid binding property of 2175 has been disputed and, because of uncertainly regarding phospholipid binding, the modeling of neutralizing mechanisms has been difficult To explore this issue, we examined the binding of 4E10 and 2175 to a broad range of lipid antigens by ELISA. 4E10 and 2F5 both bound to a variety of purified phospholipids, and 4E10 bound, but 2F5 did not bind, to cardiolipin. Both mAbs also bound to a sulfated glycolipid, sulfogalactosyl ceramide (sulfatide), and to two neutral glycolipids, galactosyl ceramide and glucosyl ceramide, but not to other galactosyl glycolipids. 4E10, but not 2175, also bound to cholesterol, although both mAbs bound to squalene. Interestingly, 4E10, but not 2F5, exhibited striking binding to lipid A, the lipid moiety of Gram-negative bacterial lipopolysaccharide. The binding properties of 4E10 to phospholipids, sulfatide, cholesterol, squalene, and lipid A were similar to those of a neutralizing murine mAb (WR304) induced by liposomes containing phosphatidylinositol phosphate and lipid A, although WR304 did not bind to neutral glycolipids. The discovery of a binding specificity of 4E10 for lipid A, a widely used vaccine adjuvant, suggests that innate immunity stimulated by lipid A could have played a role for induction of multispecific antibodies that simultaneously recognize both HIV-1 protein and lipid antigens. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:660 / 665
页数:6
相关论文
共 29 条
[1]   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].
Alam, S. Munir ;
McAdams, Mildred ;
Boren, David ;
Rak, Michael ;
Scearce, Richard M. ;
Gao, Feng ;
Camacho, Zenaido T. ;
Gewirth, Daniel ;
Kelsoe, Garnett ;
Chen, Pojen ;
Haynes, Barton F. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4424-4435
[2]  
ALVING BM, 1987, CLIN EXP IMMUNOL, V69, P403
[3]   Lipid A and liposomes containing lipid A as antigens and adjuvants [J].
Alving, Carl R. ;
Rao, Mangala .
VACCINE, 2008, 26 (24) :3036-3045
[4]   4E10 and 2F5 monoclonal antibodies: binding specificities to phospholipids, tolerance, and clinical safety issues [J].
Alving, Carl R. .
AIDS, 2008, 22 (05) :649-651
[5]   HIV-1, lipid rafts, and antibodies to liposomes: implications for anti-viral-neutralizing antibodies (Review) [J].
Alving, Carl R. ;
Beck, Zoltan ;
Karasavva, Nicos ;
Matyas, Gary R. ;
Rao, Mangala .
MOLECULAR MEMBRANE BIOLOGY, 2006, 23 (06) :453-U1
[6]   Membrane-specific antibodies induced by liposomes can simultaneously bind to HIV-1 protein, peptide, and membrane lipid epitopes [J].
Beck, Zoltan ;
Karasavvas, Nicos ;
Matyas, Gary R. ;
Alving, Carl R. .
JOURNAL OF DRUG TARGETING, 2008, 16 (7-8) :535-542
[7]   Calcium modulation of monoclonal antibody binding to phosphatidylinositol phosphate [J].
Beck, Zoltan ;
Karasavvas, Nicos ;
Tong, James ;
Matyas, Gary R. ;
Rao, Mangala ;
Alving, Carl R. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 354 (03) :747-751
[8]   Monoclonal antibodies to phosphatidylinositol phosphate neutralize human immunodeficiency virus type 1: Role of phosphate-binding subsites [J].
Brown, Bruce K. ;
Karasavvas, Nicos ;
Beck, Zoltan ;
Matyas, Gary R. ;
Birx, Deborah L. ;
Polonis, Victoria R. ;
Alving, Carl R. .
JOURNAL OF VIROLOGY, 2007, 81 (04) :2087-2091
[9]   Antibody vs. HIV in a clash of evolutionary titans [J].
Burton, DR ;
Stanfield, RL ;
Wilson, IA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (42) :14943-14948
[10]   Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41 [J].
Cardoso, RMF ;
Zwick, MB ;
Stanfield, RL ;
Kunert, R ;
Binley, JM ;
Katinger, H ;
Burton, DR ;
Wilson, IA .
IMMUNITY, 2005, 22 (02) :163-173