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).