A soluble recombinant polypeptide comprising the amino-terminal half of the extracellular region of the CD4 molecule contains an active binding site for human immunodeficiency virus.
Infection of helper T lymphocytes by human immunodeficiency virus is initiated by a specific interaction of the viral envelope glycoprotein with CD4, an integral membrane glycoprotein of the target cell. We have adapted a vaccinia virus-based mammalian cell expression system to produce variants of the CD4 molecule for structure-function studies. In this report we demonstrate that a truncated 180-amino acid fragment representing approximately the N-terminal half of the extracellular region of CD4 is found primarily in soluble form in the extracellular medium. Epitope analysis with a panel of anti-CD4 murine monoclonal antibodies indicates that the fragment reacts with those antibodies known to block the interaction between CD4 and the human immunodeficiency virus envelope glycoprotein but reacts poorly or not at all with those antibodies that do not block this interaction. We also show that the fragment forms a specific complex with a soluble form of gp120, the CD4-binding subunit of the viral envelope glycoprotein. These results indicate that this soluble CD4 fragment contains an active binding site for human immunodeficiency virus.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005110:Extracellular Space / Q000032:analysis; D006678:HIV / Q000276:immunology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D011991:Receptors, Virus; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D004247:DNA