HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4.
Although the HIV gp120 binding site of CD4 is well characterized, its interaction site with HLA class II molecules is still controversial. Sixty-seven mutations within the four extracellular domains of CD4 were examined for their effects on cell surface expression and conformational changes and for adhesion of HLA class II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells. Mutations within the gp120 binding site affected both assays similarly, indicating that the two sites fully overlap. A few additional substitutions of residues mapping on the same face of domains 1 and 2 induced decreased rosette formation. Molecular modeling studies indicated that this is likely to be the consequence of conformational changes induced by the mutations. Thus, CD4 appears to interact with HLA class II molecules mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule.
Houlgatte
R
R
Unité de Génétique Moléculaire et de Biologie du Développement UPR 420, Centre National de la Recherche Scientifique, Villejuif, France.
Scarmato
P
P
el Marhomy
S
S
Martin
M
M
Ostankovitch
M
M
Lafosse
S
S
Vervisch
A
A
Auffray
C
C
Platier-Tonneau
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites / Q000235:genetics; D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006680:HLA Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II