A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody.
An anti-gp120 monoclonal antibody (MAb), C108G (gamma 1, kappa), was isolated from a chimpanzee that had been infected with strain IIIB of human immunodeficiency virus type 1 (HIV-1IIIB) and subsequently immunized with the recombinant glycoprotein rgp160MN. This MAb is specific for the IIIB strain of HIV-1 and related clones and exhibits very potent neutralization of these viruses; e.g., 100% neutralization of approximately 8 x 10(3) infectious units of HXB2 was achieved with 125 ng of C108G per ml. Commensurate with this potent neutralizing activity, the apparent affinity of C108G for rgp160LAI was very high, i.e., approximately 3 x 10(10) liters/mol. The C108G epitope was not destroyed by reduction of gp120 disulfide bonds but was profoundly disrupted by removal of N-linked sugars from gp120. Despite the importance of a glycan(s) in forming the C108G epitope, specific binding of C108G to synthetic peptides overlapping in amino acids 162 to 169 of the V2 region was detected, albeit with an affinity approximately 2,000-fold lower than that of C108G's binding to glycosylated envelope protein. This epitope mapping correlated with results of competition assays using MAbs of known epitope specificities. To our knowledge, this is the first description of an anti-V2 MAb raised in response to HIV-1 infection. Its potent neutralizing activity and epitope specificity indicate that the V2 domain of gp120 may be an effective target of the protective immune response and, therefore, potentially an important component of HIV vaccines.
Warrier
S V
SV
Public Health Research Institute, New York, New York 10016.
Pinter
A
A
Honnen
W J
WJ
Girard
M
M
Muchmore
E
E
Tilley
S A
SA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D002679:Pan troglodytes; D011134:Polysaccharides
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides