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PDBsum entry 2aab
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Immune system
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PDB id
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2aab
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References listed in PDB file
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Key reference
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Title
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Structural basis of antigen mimicry in a clinically relevant melanoma antigen system.
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Authors
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C.C.Chang,
F.G.Hernandez-Guzman,
W.Luo,
X.Wang,
S.Ferrone,
D.Ghosh.
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Ref.
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J Biol Chem, 2005,
280,
41546-41552.
[DOI no: ]
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PubMed id
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Abstract
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Although mimics of human tumor antigens are effective immunogens to overcome
host unresponsiveness to the nominal antigen, the structural basis of this
mimicry remains poorly defined. Therefore, in this study we have characterized
the structural basis of the human high molecular weight-melanoma-associated
antigen (HMW-MAA) mimicry by the mouse anti-idiotypic (anti-id) monoclonal
antibody (mAb) MK2-23. Using x-ray crystallography, we have characterized the
three-dimensional structure of the anti-id mAb MK2-23 Fab' and shown that its
heavy chain complementarity-determining region (CDR3) (H3) and its light chain
CDR1 (L1) are closely associated. These moieties are the source of HMW-MAA
mimicry, since they display partial amino acid sequence homology along with a
similar structural fold with the HMW-MAA core protein. Furthermore, a 15-residue
peptide comprising the H3 loop of anti-id mAb MK2-23 demonstrates HMW-MAA-like
in vitro and in vivo reactivity. This peptide in conjunction with the structural
data will facilitate the characterization of the effect of the degree of antigen
mimicry on the induction of a self-antigen-specific immune response by a mimic.
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Figure 2.
FIGURE 2. Crystal structure of an anti-id mAb MK2-23 Fab'
fragment at 2. 5 Å resolution shown in ribbon diagram. A,
the CDR loops of the light (CDR1L) (L1) (green) and heavy
(CDR3H) (H3) (yellow) chains are shown as labeled. The boxed
area is shown in stereo images (B), detailing the secondary and
tertiary structures of anti-id mAb MK2-23 L1 and H3 and their
final electron density maps. Hydrogen bonds are shown by dotted
lines.
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Figure 3.
FIGURE 3. Three-dimensional alignment of five available
anti-id mAb: 409.5.3 (PDB code 1AIF), 6A6 (PDB code 1PG7), E225
(PDB code 1CIC [PDB]
), E5.2 (PDB code 1DVF), and MK2-23 (this study), two
anti-anti-id mAb: 131 (PDB code 2CK0) and GH1002 (PDB code 1GHF)
and two randomly selected idiotypic mAb: Mopc21 (PDB code 1IGC),
and R24 (PDB code 1R24 [PDB]
) by using least squares fitting of the conserved residues.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
41546-41552)
copyright 2005.
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