       Document 0605
 DOCN  M9620605
 TI    Human complement proteins C3b, C4b, factor H and properdin react with
       specific sites in gp120 and gp41, the envelope proteins of HIV-1.
 DT    9602
 AU    Stoiber H; Schneider R; Janatova J; Dierich MP; Ludwig Boltzmann
       Institute for AIDS Research, University of; Innsbruck, Austria.
 SO    Immunobiology. 1995 Jun;193(1):98-113. Unique Identifier : AIDSLINE
       MED/96100682
 AB    Recently we reported the basic phenomenon of an interaction between the
       envelope glycoproteins of HIV-1 gp120 and gp41 and components of the
       human complement system, i.e. activated C4 (C4b) and activated C3 (C3b)
       and the complement regulator proteins factor H and properdin. In this
       study we analyze these interactions in detail. Using 46 overlapping
       peptides of gp120 attached to microtiter plates, binding of activated
       human C3 to 6 regions in gp120 was found (aa 100-129, 161-190, 231-250,
       301-328, 410-449, 470-499). In competition assays with soluble peptides,
       representatives of four of these regions were capable to partially
       inhibit C3b binding to immobilized gp120. Activated human C4 interacted
       only with peptides covering aa 410-449, but both in direct binding
       assays and fluid phase inhibition studies. The multi-reactivity of gp120
       with C3b was also supported by the fact that gp120 agglutinated
       erythrocytes coated with C3b. Guided by partial aa sequence homology of
       gp120 and human C4b binding protein (C4bp) as well as human properdin we
       detected binding of anti-properdin to aa 100-129 in gp120 and of
       anti-C4bp to aa 410-449 in gp120. This cross-reactivity was also
       confirmed by a monoclonal antibody directed against aa 416-443 of gp120,
       which could be shown to bind C4bp. Interestingly, aa 310-328, part of
       the V3-loop, were found to show an aa sequence similarity to human
       complement receptor type 3 (alpha-chain). Consequently, of the 4 (or
       possibly 6) interaction sites of gp120 with activated human C3, 3 may
       bind due to imitation of either properdin, CR3 or C4bp. In addition to
       C4b and C3b, we detected interaction of factor H with gp120; it
       selectively bound to aa 102-129. Using 14 overlapping peptides of gp41
       attached to plates, we identified 4 areas in gp-41 (aa 561-585, 587-605,
       615-635, 651-675) which bound human factor H. All of them except the
       first region partially inhibited factor H binding to gp41 in competition
       assays with soluble peptides. Properdin bound only to 2 regions (aa
       584-614, 651-675). The first 3 sites in gp41 were already shown by us to
       share homology to sites in human C3. The region around aa 651-675 now
       also turned out to be similar to human C3. These data demonstrate that
       the interaction of both, gp120 and gp41, with the complement system is
       polyvalent and complex.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Amino Acid Sequence  Antibodies, Monoclonal/METABOLISM  Binding
       Sites/IMMUNOLOGY  Complement/*METABOLISM  Complement Factor H/METABOLISM
       Complement 3b/METABOLISM  Complement 4b/IMMUNOLOGY/METABOLISM  Cross
       Reactions  Hemagglutination/IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/BLOOD/IMMUNOLOGY/*METABOLISM  HIV Envelope Protein
       gp41/*METABOLISM  HIV-1/*METABOLISM  Molecular Sequence Data  Peptide
       Mapping  Properdin/IMMUNOLOGY/METABOLISM  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).

