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M9650327.TXT
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1996-03-09
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Document 0327
DOCN M9650327
TI The gp120 envelope of HIV-1 binds peptides in a similar manner to human
leukocyte antigens.
DT 9605
AU Sheikh MJ; Ongradi J; Austen BM; Dalgleish AG; Department of Cellular
and Molecular Sciences, St George's; Hospital Medical School, London,
UK.
SO AIDS. 1995 Nov;9(11):1229-35. Unique Identifier : AIDSLINE MED/96126176
AB OBJECTIVE: All the conserved regions of HIV gp120 have at least some
partial homology with human leukocyte antigen (HLA) class I or class II.
One functional similarity is the ability of gp120 and HLA class II to
bind CD4. Given the close association between HIV-induced disease and
the amount of immune activation and anergy, features closely associated
with chronic allogenic stimulation, we asked whether gp120 shared any
other properties of HLA, in this case the ability to bind peptides.
DESIGN: T-cell epitope peptides known to bind to soluble HLA class I or
class II were photolabelled and made radioactive. Cross-linking of
modified peptides to soluble HLA class I, II and gp120 was activated by
ultraviolet light and analysed by sodium dodecylsulphate-polyacrylamide
gel electrophoresis. RESULTS: A signal peptide binding to HLA class I
and a haemagglutinin peptide that binds to HLA class II were found to
bind soluble gp120 specifically; binding and cross-linking could be
competed out with excess of the unmodified peptides but not unrelated
control peptides. Molecular modelling of gp120 suggests shared anchor
sites for peptides binding to both HLA and gp120 soluble molecules.
CONCLUSIONS: The ability to bind these two peptides suggests that gp120
has a peptide-binding site of broad specificity, which if functional in
vivo, could compete with normal peptide loading of major
histocompatibility complex (MHC) class I and/or class II peptides, as
well as aberrantly stimulate the T-cell receptor (by virtue of its
potential to be mistaken for an allogenic MHC/peptide complex),
resulting in immune activation, anergy and apoptosis in susceptible
hosts.
DE Amino Acid Sequence Binding, Competitive Epitopes/METABOLISM Human
HIV Envelope Protein gp120/*METABOLISM *HIV-1 HLA Antigens/*METABOLISM
Molecular Sequence Data Peptides/CHEMICAL SYNTHESIS/*METABOLISM
Support, Non-U.S. Gov't T-Lymphocytes/IMMUNOLOGY/*METABOLISM JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).