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1996-02-27
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Document 0239
DOCN M9630239
TI Presentation of HIV V3 loop epitopes for enhanced antigenicity,
immunogenicity and diagnostic potential.
DT 9603
AU Fontenot JD; VanCott TC; Parekh BS; Pau CP; George JR; Birx DL;
Zolla-Pazner S; Gorny MK; Gatewood JM; Theoretical Biology and
Biophysics and Life Sciences Division,; Los Alamos National Laboratory,
New Mexico.
SO AIDS. 1995 Oct;9(10):1121-9. Unique Identifier : AIDSLINE MED/96098127
AB OBJECTIVE: To evaluate the immunological properties of a panel of human
mucin MUC1/HIV V3 loop chimeras. DESIGN: The immunodominant epitope of
MUC1 (APDTR) was found to be structurally isomorphous with the tip of
the principle neutralizing determinant (PND) of HIV-1 (MN) (GPGRA). A
panel of 120 residue, six tandem repeat (TR) and 60 residue, three TR
chimeric antigens were constructed in which the repeating MUC1 epitope
is replaced by HIV-1 PND. Each 20 residue TR contains one PND epitope.
The PND of HIV-1 is presented in the native beta-turn conformation at
the crest of each repeating knob structure of the mucin-like protein.
METHODS: The antigenicity of the chimeric antigens were compared using
enzyme-linked immunosorbent assay (ELISA) and HIV-infected patient sera.
Structural effects of antibody-antigen interactions were determined
using surface plasmon resonance, with human monoclonal antibodies,
chimeric antigens and the cyclic and linear V3 loops. Immunogenicity of
three versus six TR was measured in mice. RESULTS: Nine residues of the
HIV PND substituted into the mucin backbone were equivalent to the 36
residue cyclic V3 loop in ELISA. The 120 residue antigens induced high
titer, immunoglobulin (Ig) M and IgG, and HIV-specific antibodies in
mice. CONCLUSIONS: MUC1/V3 chimeras efficiently detect HIV-specific
antibodies in patient sera. Multivalent presentation of the PND is
advantageous for higher affinity antibody-antigen interactions and for
inducing HIV-specific IgM and IgG antibodies.
DE Amino Acid Sequence Animal Antibodies, Monoclonal Antibody
Specificity AIDS Serodiagnosis/METHODS Chimeric Proteins/IMMUNOLOGY
Female Human HIV Antibodies/*IMMUNOLOGY/METABOLISM HIV Envelope
Protein gp120/CHEMISTRY/*IMMUNOLOGY/METABOLISM HIV-1/*IMMUNOLOGY
IgG/BIOSYNTHESIS IgM/BIOSYNTHESIS Immunodominant
Epitopes/ANALYSIS/*IMMUNOLOGY Kinetics Mice Mice, Inbred BALB C
Molecular Sequence Data Mucins/CHEMISTRY/IMMUNOLOGY Peptide
Fragments/CHEMISTRY/*IMMUNOLOGY/METABOLISM Repetitive Sequences,
Nucleic Acid 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).