title: Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1.
abstract: Monoclonal antibodies (MAbs) to defined peptide epitopes on gp120 from human immunodeficiency virus type 1 were used to investigate the involvement of their epitopes in gp120 binding to the CD4 receptor. Recombinant vaccinia viruses were constructed that expressed either full-length gp120 (v-ED6), or a truncated gp120 lacking 44 amino acids at the carboxyl terminus (v-ED4). Binding of these glycoproteins to the CD4 receptor was detected directly with metabolically labeled gp120 or indirectly with the gp120 MAbs. Truncated gp120 from v-ED4 bound to CD4-positive cells less than 1/12 as well as gp120 from v-ED6, indicating that the C-terminal region of gp120, which is conserved in numerous isolates of human immunodeficiency virus type 1, is critical for CD4 binding. However, MAb 110-1, which recognizes a peptide contained in the region deleted from v-ED4 (amino acids 489 through 511), did not inhibit binding of gp120 to CD4. MAb 110-1 also reacted with gp120 bound to the CD4 receptor, indicating that the epitope for this antibody does not directly interact with CD4. A second MAb, 110-4, which recognizes a peptide epitope located between amino acids 303 and 323 and has potent viral neutralizing activity, also bound to gp120 on the CD4 receptor. Furthermore, pretreatment of gp120 with MAb 110-4 at concentrations approximately 1,000-fold higher than those required for complete virus neutralization inhibited subsequent CD4 binding by only about 65%. Taken together, these data suggest that neutralization mediated by antibody 110-4 does not result from binding of this MAb to the CD4-binding site of gp120.
authors: Oncogen, Seattle, Washington 98121.
authors: P S
authors: PS
authors: Linsley
authors: J A
authors: JA
authors: Ledbetter
authors: E
authors: E
authors: Kinney-Thomas
authors: S L
authors: SL
authors: Hu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006678:HIV / Q000276:immunology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120; D006801:Humans; D011233:Precipitin Tests; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins