title: Localized conformational changes in the N-terminal domain of CD4 identified in competitive binding assay of monoclonal antibodies and HIV-1 envelope glycoprotein.
abstract: The CD4 antigen is established as a major cellular receptor for the human immunodeficiency virus (HIV). Previous studies have suggested that certain anti-CD4 monoclonal antibodies (MAbs) can inhibit or enhance the binding of the viral envelope glycoprotein gp120 to CD4 by allosteric effects. In the study reported here, 17 anti-CD4 MAbs were tested for their ability to influence the binding of each other to recombinant soluble CD4 in a solid-phase radioimmunoassay. Marked enhancement of binding between specific pairs of MAbs was seen, as well as inhibition or lack of interaction. Enhancement was seen less often when CD4+ cells were used as the target antigen. Information on patterns of enhancement and inhibition permitted grouping of MAbs on the basis of epitope specificity, and this grouping was in agreement with published findings based on X-ray crystallographic studies. These results demonstrate connectivity between epitopes in the first domain of recombinant CD4 and suggest a high degree of flexibility of surface structure. These findings may be of physiological significance both in the normal function of CD4 and in the interaction of CD4 with HIV. The data have implications for research or therapeutic strategies based on recombinant CD4 or CD4 mutants and highlight the problems of interpreting experimental findings based on abrogation of MAb binding.
authors.affiliation: Division of Immunology, Clinical Research Centre, Harrow, England.
authors.forename: L
authors.initials: L
authors.lastname: Walker
authors.forename: D
authors.initials: D
authors.lastname: Wilks
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: J
authors.initials: J
authors.lastname: Habeshaw
authors.forename: A
authors.initials: A
authors.lastname: Dalgleish
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D011487:Protein Conformation; D011863:Radioimmunoassay
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120