OLIGOMERIZATION OF CD4 IS REQUIRED FOR STABLE BINDING TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS BUT NOT FOR INTERACTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS GP120

Previous studies have failed to detect an interaction between monomeri c soluble CD4 (sCD4) and class II major histocompatibility complex (MH C) proteins, suggesting that oligomerization of CD4 on the cell surfac e may be required to form a stable class II MHC binding site. To test this possibility, we transfected the F43I CD4 mutant, which is incapab le of binding to class II MHC or human immunodeficiency virus (HIV) gp 120, into COS-7 cells together with wild-type CD4 (wtCD4). Expression of F43I results in a dominant negative effect: no class II MHC binding is observed even though wtCD4 expression is preserved. Apparently, F4 3I associates with wtCD4 oligomers and interferes with the formation o f functional class II MHC binding structures. In contrast, F43I does n ot affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4 monomer. By production and characterization of chimeric CD4 mole cules, rye show that domains 3 and/or 4 appear to be involved in oligo merization. Several models of the CD4-class II MHC interaction are off ered, including the possibility that one or two CD4 molecules initiall y interact with class II MHC dimers and further associate to create la rger complexes important for facilitating T-cell receptor crosslinking .