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M9460663.TXT
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1994-06-25
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Document 0663
DOCN M9460663
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).