HLA CLASS-II ANTIGENS AND THE HIV ENVELOPE GLYCOPROTEIN GP120 BIND TOTHE 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. S ixty-seven mutations within the four extracellular domains of CD4 were examined for their effects on cell surface expression and conformatio nal changes and for adhesion of HLA class II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells. Mutations within t he gp120 binding site affected both assays similarly, indicating that the two sites fully overlap. A few additional substitutions of residue s mapping on the same face of domains 1 and 2 induced decreased rosett e formation. Molecular modeling studies indicated that this is likely to be the consequence of conformational changes induced by the mutatio ns. Thus, CD4 appears to interact with HLA class II molecules mainly t hrough the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule.