Document 0282
 DOCN  M9460282
 TI    The construction and characterization of poliovirus antigen chimeras
       presenting defined regions of the human T lymphocyte marker CD4.
 DT    9408
 AU    Rose C; Andrews W; Ferguson M; McKeating J; Almond J; Evans D;
       Department of Microbiology, University of Reading, Whiteknights,; U.K.
 SO    J Gen Virol. 1994 May;75 ( Pt 5):969-77. Unique Identifier : AIDSLINE
       MED/94231176
 AB    Defined regions of the CDR2-like region of the T cell antigen CD4 that
       are implicated in the binding of the surface glycoprotein (gp120) of
       human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have
       been engineered in place of antigenic site 1 of Sabin type 1 poliovirus.
       The antigenic properties of the recovered chimeric virus particles were
       investigated using monoclonal antibodies (MAbs) and polyclonal serum to
       CD4. None of the MAbs tested neutralized the chimeras, presumably
       because they are directed against conformational determinants of the V1
       domain of CD4. In contrast, the three antigen chimeras were neutralized
       by polyclonal serum to CD4, which suggested that the CD4-derived
       sequences were presented in a relevant conformation. A panel of six MAbs
       were raised against one of the chimeras, and the epitopes were mapped by
       the selection of neutralization-resistant mutants and
       cross-neutralization studies. Five of the six MAbs reacted with soluble
       CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the
       surface of HeLa cells. The high affinity interaction between gp120 and
       sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did
       not interact with gp120. These results demonstrate that poliovirus can
       be used as an epitope expression vector for the presentation of
       sequences in an immunodominant location on the virus particle which
       adopt a native or near-native conformation, and supports the findings of
       previous studies involving the presentation of epitopes derived from
       pathogens.
 DE    Amino Acid Sequence  Antibodies, Monoclonal  Antibody Formation
       Antibody Specificity  Antigens, CD4/GENETICS/*IMMUNOLOGY/METABOLISM
       Base Sequence  Capsid/GENETICS/*IMMUNOLOGY  Chimeric
       Proteins/*IMMUNOLOGY  HIV Envelope Protein gp120/IMMUNOLOGY/METABOLISM
       Molecular Sequence Data  Mutation  Neutralization Tests  Polioviruses,
       Human 1-3/GROWTH & DEVELOPMENT/GENETICS/*IMMUNOLOGY  Protein Binding
       Support, Non-U.S. Gov't  JOURNAL ARTICLE

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