Document 0507
 DOCN  M9480507
 TI    Recognition properties of a panel of human recombinant Fab fragments to
       the CD4 binding site of gp120 that show differing abilities to
       neutralize human immunodeficiency virus type 1.
 DT    9410
 AU    Roben P; Moore JP; Thali M; Sodroski J; Barbas CF 3rd; Burton DR;
       Department of Immunology, Scripps Research Institute, La Jolla,;
       California 92037.
 SO    J Virol. 1994 Aug;68(8):4821-8. Unique Identifier : AIDSLINE
       MED/94309144
 AB    Six recombinant human Fab fragments that were derived from the same
       human immunodeficiency virus type 1 (HIV-1)-infected individual and are
       directed against the CD4 binding site (CD4bs) of the gp120 envelope
       glycoprotein were studied. A range of neutralizing activity against the
       HIV-1 (HXBc2) isolate was observed, with Fab b12 exhibiting the greatest
       potency among the Fabs tested. The neutralizing potency of Fab b12 was
       better than that of monoclonal whole antibodies directed against the
       third variable (V3) region of gp120. To explore the basis for the
       efficient neutralizing activity of b12, the recognition of a panel of
       HIV-1 gp120 mutants by the six Fabs was studied. The patterns of
       sensitivity to particular gp120 amino acid changes were similar for all
       six Fabs to those seen for anti-CD4bs monoclonal antibodies derived from
       HIV-1-infected individuals by conventional means. In addition,
       recognition by Fab b12 demonstrated an atypical sensitivity to changes
       in the V1 and V2 variable regions. Next, the binding of the Fabs to
       monomeric gp120 and to the envelope glycoprotein complex was examined.
       Neither the binding properties of the b12 Fab to monomeric gp120 nor the
       ability of the Fab to compete with soluble CD4 for monomeric gp120
       binding appeared to account for the greater neutralizing potency.
       However, both quantitative and qualitative differences between the
       binding of b12 and that of less potent Fabs to the cell surface envelope
       glycoprotein complex were observed. Relative to less potently
       neutralizing Fabs, Fab b12 exhibited a higher affinity for a
       subpopulation of cell surface envelope glycoproteins, the conformation
       of which was best approximated by the mature gp120 glycoprotein.
       Apparently, subtle differences in the gp120 epitope recognized allow
       some members of the group of anti-CD4bs antibodies to bind to the
       functionally relevant envelope glycoprotein complex and to neutralize
       virus more efficiently.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Antibody Affinity  Antigenic
       Determinants  Antigens, CD4/*METABOLISM  Binding Sites  Cell Line
       Cloning, Molecular  Human  HIV Antibodies/IMMUNOLOGY  HIV Envelope
       Protein gp120/GENETICS/*IMMUNOLOGY/METABOLISM  HIV
       Infections/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY  IgG/IMMUNOLOGY
       Immunoglobulins, Fab/*IMMUNOLOGY  Mutation  Neutralization Tests
       Recombinant Proteins/IMMUNOLOGY  Solubility  Support, Non-U.S. Gov't
       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).