       Document 0276
 DOCN  M9460276
 TI    Effect of antibody valency on interaction with cell-surface expressed
       HIV-1 and viral neutralization.
 DT    9404
 AU    Cavacini LA; Emes CL; Power J; Duval M; Posner MR; Department of
       Medicine, New England Deaconess Hospital, Boston,; MA 02215.
 SO    J Immunol. 1994 Mar 1;152(5):2538-45. Unique Identifier : AIDSLINE
       MED/94179837
 AB    F(ab) and F(ab')2 fragments of the human mAb, F105, were compared to
       intact IgG1 for binding to the CD4 binding site of HIV-1/gp120 on the
       surface of infected cells and viral neutralization. F105 IgG1 and
       F(ab')2 bound to IIIB, MN, and RF infected cells and neutralized these
       strains in an identical fashion, whereas strain-specific differences
       were observed in F(ab) activity. Although F105 F(ab) bound with
       equivalent affinity to IIIB-infected cells, there was a 4- to 10-fold
       decrease in the neutralization of IIIB by monovalent F(ab) compared to
       the bivalent molecules. F105 F(ab) demonstrated both diminished binding
       and neutralization of the MN strain and failed to bind or neutralize the
       RF strain. When cooperativity of V3 loop antibody (V3ab) with F105 IgG
       and fragments was examined, the binding of F105 IgG and F(ab')2 to
       IIIB-, MN-, or RF-infected cells was modestly enhanced by V3ab; viral
       neutralization was substantially enhanced by the combination of V3ab and
       F105 IgG and F(ab')2. The combination of F105 F(ab) with V3ab also
       resulted in significant cooperative neutralization of IIIB and MN, but
       the lack of F105 F(ab) binding and neutralization of RF was unaltered by
       V3ab. These results suggest that bivalent interaction may be important
       in binding and neutralization of virus, and support the notion that this
       interaction may depend on conformational changes in oligomeric gp120 on
       intact virions and cell surface rather than on affinity or steric
       effects.
 DE    Antibodies, Monoclonal  Antigenic Determinants  Cell Line  Cell
       Membrane/IMMUNOLOGY/MICROBIOLOGY  Human  HIV Antibodies/*METABOLISM  HIV
       Envelope Protein gp120/IMMUNOLOGY  HIV
       Infections/IMMUNOLOGY/MICROBIOLOGY  HIV-1/*IMMUNOLOGY  IgG/METABOLISM
       Immunoglobulins, Fab/METABOLISM  Neutralization Tests  Receptors,
       HIV/IMMUNOLOGY  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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

