Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.
Interaction with the CD4 receptor enhances the exposure on the human immunodeficiency type 1 gp120 exterior envelope glycoprotein of conserved, conformation-dependent epitopes recognized by the 17b and 48d neutralizing monoclonal antibodies. The 17b and 48d antibodies compete with anti-CD4 binding antibodies such as 15e or 21h, which recognize discontinuous gp120 sequences near the CD4 binding region. To characterize the 17b and 48d epitopes, a panel of human immunodeficiency virus type 1 gp120 mutants was tested for recognition by these antibodies in the absence or presence of soluble CD4. Single amino acid changes in five discontinuous, conserved, and generally hydrophobic regions of the gp120 glycoprotein resulted in decreased recognition and neutralization by the 17b and 48d antibodies. Some of these regions overlap those previously shown to be important for binding of the 15e and 21h antibodies or for CD4 binding. These results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies.
Thali
M
M
Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Moore
J P
JP
Furman
C
C
Charles
M
M
Ho
D D
DD
Robinson
J
J
Sodroski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D000939:Epitopes; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D046911:Macromolecular Substances; D011991:Receptors, Virus; D011994:Recombinant Proteins