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PDBsum entry 3cvi
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Immune system
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PDB id
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3cvi
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References listed in PDB file
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Key reference
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Title
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How a t cell receptor-Like antibody recognizes major histocompatibility complex-Bound peptide.
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Authors
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T.Mareeva,
E.Martinez-Hackert,
Y.Sykulev.
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Ref.
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J Biol Chem, 2008,
283,
29053-29059.
[DOI no: ]
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PubMed id
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Abstract
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We determined the crystal structures of the T cell receptor (TCR)-like antibody
25-D1.16 Fab fragment bound to a complex of SIINFEKL peptide from ovalbumin and
the H-2K(b) molecule. Remarkably, this antibody directly "reads" the structure
of the major histocompatibility complex (MHC)-bound peptide, employing the
canonical diagonal binding mode utilized by most TCRs. This is in marked
contrast with another TCR-like antibody, Hyb3, bound to melanoma peptide MAGE-A1
in association with HLA-A1 MHC class I. Hyb3 assumes a non-canonical orientation
over its cognate peptide-MHC and appears to recognize a conformational epitope
in which the MHC contribution is dominant. We conclude that TCR-like antibodies
can recognize MHC-bound peptide via two different mechanisms: one is similar to
that exploited by the preponderance of TCRs and the other requires a
non-canonical antibody orientation over the peptide-MHC complex.
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Figure 2.
Positioning of 25-D1.16 and Hyb3 Fab fragments of TCR-like
antibodies over cognate pMHC complexes. The left panel shows the
25-D1.16-pOV8-K^b complex, and the right panel shows the
MAGE-A1-HLA-A1 complex. Fab heavy and light chains are colored
light and dark gray, respectively. The MHC heavy chain and
β[2]m are shown in cyan and dark blue, respectively. 25-D1.16
assumes an orientation that is common for TCRs, with the CDR1
and CDR2 loops contacting K^b helices and the CDR3 loops forming
direct contacts with the peptide. MAGE-A1-HLA-A1-bound Hyb3 has
an atypical orientation, tilting toward helix α[1] without
contacting helix α[2] and forming few direct contacts with the
peptide.
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Figure 5.
Schematic representation of the positioning of 25-D1.16 and
Hyb3 antibodies. 25-D1.16 and KB5-C20 TCR (11) utilize a very
similar mode of recognition of MHC-bound peptide that is
distinct from that used by Hyb3 antibodies (4). Red and green
vectors show virtually identical orientations of 25-D1.16 and
KB5-C20 TCR; the dark blue vector indicates a profoundly
different orientation of Hyb3; and the black vector indicates
peptide positioning in the binding groove of both H2-K^b and
HLA-A1 MHC-I proteins.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2008,
283,
29053-29059)
copyright 2008.
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