       Document 0289
 DOCN  M95A0289
 TI    Oligomerization of CD4 is required for stable binding to class II major
       histocompatibility complex proteins but not for interaction with human
       immunodeficiency virus gp120.
 DT    9510
 AU    Sakihama T; Smolyar A; Reinherz EL; Laboratory of Immunobiology,
       Dana-Farber Cancer Institute,; Boston, MA, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6444-8. Unique Identifier :
       AIDSLINE MED/95327663
 AB    Previous studies have failed to detect an interaction between monomeric
       soluble CD4 (sCD4) and class II major histocompatibility complex (MHC)
       proteins, suggesting that oligomerization of CD4 on the cell surface may
       be required to form a stable class II MHC binding site. To test this
       possibility, we transfected the F43I CD4 mutant, which is incapable of
       binding to class II MHC or human immunodeficiency virus (HIV) gp120,
       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, F43I
       associates with wtCD4 oligomers and interferes with the formation of
       functional class II MHC binding structures. In contrast, F43I does not
       affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4
       monomer. By production and characterization of chimeric CD4 molecules,
       we show that domains 3 and/or 4 appear to be involved in
       oligomerization. Several models of the CD4-class II MHC interaction are
       offered, including the possibility that one or two CD4 molecules
       initially interact with class II MHC dimers and further associate to
       create larger complexes important for facilitating T-cell receptor
       crosslinking.
 DE    Animal  Antigens, CD4/BIOSYNTHESIS/CHEMISTRY/*METABOLISM  Cell Line
       Cercopithecus aethiops  Comparative Study  Flow Cytometry
       Histocompatibility Antigens Class II/IMMUNOLOGY/*METABOLISM  Human  HIV
       Envelope Protein gp120/IMMUNOLOGY/*METABOLISM  HLA-D
       Antigens/IMMUNOLOGY/*METABOLISM  Lymphocyte Transformation
       Macromolecular Systems  Models, Immunological  Protein Binding
       Recombinant Proteins/BIOSYNTHESIS/CHEMISTRY/METABOLISM  Support, U.S.
       Gov't, P.H.S.  T-Lymphocytes/*IMMUNOLOGY  Transfection  Tumor Cells,
       Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

