Epitope map of human immunodeficiency virus type 1 gp41 derived from 47 monoclonal antibodies produced by immunization with oligomeric envelope protein

被引:105
作者
Earl, PL [1 ]
Broder, CC [1 ]
Doms, RW [1 ]
Moss, B [1 ]
机构
[1] UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104
关键词
D O I
10.1128/JVI.71.4.2674-2684.1997
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The biologically relevant form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein protein is oligomeric, with the major points of contact between oligomeric partners located in the ectodomain of gp41. To identify and map conserved epitopes and regions in gp41 where structure is influenced by quaternary interactions, we used a panel of 38 conformation-dependent and 9 conformation-independent anti-gp41 monoclonal antibodies (MAbs) produced by immunization of mice with oligomeric Env protein. By cross-competition experiments using these MAbs and several others previously described, six distinct antigenic determinants were identified and mapped. Three of these determinants are conformational in nature and dependent in part on Env oligomeric structure. MAbs to two of these determinants were broadly cross-reactive with Env proteins derived from primary virus strains. The prevalence of antibodies in HIV-1-positive human sera to the antigenic determinants was determined by the ability of such sera to block binding of MAbs to Env protein. Strong blocking activity that correlated with cross-reactivity was found.
引用
收藏
页码:2674 / 2684
页数:11
相关论文
共 56 条
  • [1] Human antibody responses to HIV type 1 glycoprotein 41 cloned in phage display libraries suggest three major epitopes are recognized and give evidence for conserved antibody motifs in antigen binding
    Binley, JM
    Ditzel, HJ
    Barbas, CF
    Sullivan, N
    Sodroski, J
    Parren, PWHI
    Burton, DR
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1996, 12 (10) : 911 - 924
  • [2] ANTIGENIC IMPLICATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE QUATERNARY STRUCTURE - OLIGOMER-SPECIFIC AND OLIGOMER-SENSITIVE MONOCLONAL-ANTIBODIES
    BRODER, CC
    EARL, PL
    LONG, D
    ABEDON, ST
    MOSS, B
    DOMS, RW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) : 11699 - 11703
  • [3] BRODER CC, 1996, METHOD MOL BIOL, V62, P173
  • [4] BRODER CC, UNPUB
  • [5] BUCHACHER A, 1992, VACCINES 92 : MODERN APPROACHES TO NEW VACCINES INCLUDING PREVENTION OF AIDS, P191
  • [6] GENERATION OF HUMAN MONOCLONAL-ANTIBODIES AGAINST HIV-1 PROTEINS - ELECTROFUSION AND EPSTEIN-BARR-VIRUS TRANSFORMATION FOR PERIPHERAL-BLOOD LYMPHOCYTE IMMORTALIZATION
    BUCHACHER, A
    PREDL, R
    STRUTZENBERGER, K
    STEINFELLNER, W
    TRKOLA, A
    PURTSCHER, M
    GRUBER, G
    TAUER, C
    STEINDL, F
    JUNGBAUER, A
    KATINGER, H
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1994, 10 (04) : 359 - 369
  • [7] CHAKRABARTI S, UNPUB
  • [8] A MOLECULAR CLASP IN THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 TM PROTEIN DETERMINES THE ANTI-HIV ACTIVITY OF GP41 DERIVATIVES - IMPLICATION FOR VIRAL FUSION
    CHEN, CH
    MATTHEWS, TJ
    MCDANAL, CB
    BOLOGNESI, DP
    GREENBERG, ML
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (06) : 3771 - 3777
  • [9] NEUTRALIZATION OF DIVERGENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS AND PRIMARY ISOLATES BY IAM-41-2F5, AN ANTI-GP41 HUMAN MONOCLONAL-ANTIBODY
    CONLEY, AJ
    KESSLER, JA
    BOOTS, LJ
    TUNG, JS
    ARNOLD, BA
    KELLER, PM
    SHAW, AR
    EMINI, EA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) : 3348 - 3352
  • [10] C-TERMINAL FRAGMENTS OF GP120 AND SYNTHETIC PEPTIDES FROM 5 HTLV-III STRAINS - PREVALENCE OF ANTIBODIES TO THE HTLV-III-MN ISOLATE IN INFECTED INDIVIDUALS
    DEVASH, Y
    MATTHEWS, TJ
    DRUMMOND, JE
    JAVAHERIAN, K
    WATERS, DJ
    ARTHUR, LO
    BLATTNER, WA
    RUSCHE, JR
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1990, 6 (03) : 307 - 316