Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4.
Animals immunized with the human immunodeficiency virus type 1 gp160 glycoprotein or certain recombinant envelope components develop potent virus-neutralizing activity. This activity is principally due to antibodies directed toward a hypervariable region of gp120 between cysteine residues 302 and 337 and is virus isolate specific. These antisera, as well as two neutralizing monoclonal antibodies directed against the same hypervariable sequence, do not appreciably block gp120 from binding CD4. In contrast, serum samples from infected humans possess high titers of antibodies that block gp120-CD4 binding; these titers approximately correlate with the serum neutralization titers. Our results suggest that there are at least two targets on the envelope glycoprotein for virus neutralization. The target responsible for the broader neutralizing activity of human serum may be a conserved region of gp120 involved in CD4 binding. The antibodies directed at the hypervariable region of the envelope inhibit a different step in virus infection which is subsequent to receptor binding. The extent to which these two different epitopes of gp120 may be involved in protection against human immunodeficiency virus infection is discussed.
Skinner
M A
MA
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Langlois
A J
AJ
McDanal
C B
CB
McDougal
J S
JS
Bolognesi
D P
DP
Matthews
T J
TJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000915:Antibody Affinity; D002459:Cell Fusion; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000502:physiology*; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D009500:Neutralization Tests; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000276:immunology*; D012191:Retroviridae Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007106:Immune Sera; D015728:Receptors, HIV; D011991:Receptors, Virus; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins