Amino acid residues of the human immunodeficiency virus type I gp120 critical for the binding of rat and human neutralizing antibodies that block the gp120-sCD4 interaction.
We have characterized the discontinuous epitopes recognized by two rat and three human neutralizing monoclonal antibodies (mAb) by examining the effect of single amino acid changes in conserved residues of gp120 on mAb recognition. A human mAb derived from an infected individual, 448D, and two rat mAbs, 39.13g and 39.3b, respectively, derived by immunization with native recombinant gp120, recognize similar epitopes. Recognition of the envelope glycoproteins by these mAbs was affected by changes in gp120 amino acid residues 88, 113, 117, 257, 368, or 370. The gp120 amino acids 257, 368, and 370 have previously been reported to be important for CD4 binding, which is consistent with the ability of these mAbs to block the gp120-CD4 interaction. Residues 88, 113, and 117 are not thought to be important for CD4 binding, suggesting that the antibody epitopes overlap, but are distinct from, the CD4 binding region. We also found that some alterations in gp120 residues 88, 117, 368, or 421 reduced the ability of polyclonal sera from HIV-1-infected individuals to inhibit the interaction of the mutant gp120 glycoproteins with soluble CD4. Thus, changes in the HIV-1 gp120 glycoprotein that minimally affect the receptor binding may allow escape from neutralizing antibodies directed against the CD4 binding region.
McKeating
J A
JA
Institute of Cancer Research, Chester Beatty Laboratories, London, U.K.
Thali
M
M
Furman
C
C
Karwowska
S
S
Gorny
M K
MK
Cordell
J
J
Zolla-Pazner
S
S
Sodroski
J
J
Weiss
R A
RA
D000596:Amino Acids / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009500:Neutralization Tests; D051381:Rats
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120