The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4.
CD4, a cell-surface glycoprotein expressed on a subset of T-cells and macrophages, serves as the receptor for the human immunodeficiency virus (HIV) (reviewed in ref. 1), binding to the HIV envelope glycoprotein, gp120 with high affinity. Attempts to block infection in vivo by raising antibodies against gp120 have failed, probably because these antibodies have insufficient neutralizing activity. In addition, because of the extensive polymorphism of gp120 in different isolates of HIV, antibodies raised against one HIV isolate are only weakly effective against others. Because interaction with CD4 is essential for infectivity by all isolates of HIV, an agent that could mimic CD4 in its ability to bind to gp120, such as a peptide or monoclonal antibody, might block infection by a wide spectrum of isolates. To aid the identification of such a ligand we have defined regions of CD4 that are required for binding to gp120. Although human CD4 is similar to mouse CD4 in amino-acid sequence (55% identity, ref. 6) and structure, we have found that the murine protein fails to bind detectably to gp120 and have exploited this finding to study binding of gp120 to mouse-human chimaeric CD4 molecules. These studies show that amino-acid residues within the amino-terminal immunoglobulin-like domain of human CD4 are involved in binding to gp120 as well as to many anti-CD4 monoclonal antibodies.
Landau
N R
NR
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Warton
M
M
Littman
D R
DR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006678:HIV / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D011991:Receptors, Virus; D014759:Viral Envelope Proteins