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PDBsum entry 1ffp
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Immune system/signaling protein
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PDB id
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1ffp
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Peptidic termini play a significant role in tcr recognition.
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Authors
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B.Wang,
A.Sharma,
R.Maile,
M.Saad,
E.J.Collins,
J.A.Frelinger.
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Ref.
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J Immunol, 2002,
169,
3137-3145.
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PubMed id
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Abstract
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TCR recognition of class I MHC is dependent on the composition of the antigenic
peptide and the MHC. Single amino acid substitutions in either the MHC or the
peptide may dramatically alter recognition. While the major interactions between
TCR and the peptide/MHC complex appear to be focused on the
complementarity-determining region (CDR)3, it is also clear from the cocrystal
structure of class I MHC and TCR that the amino and carboxyl ends of the peptide
may play a role through interactions with the CDR1. In this work we show that
gp33 variants substituted at the peptidic termini at the putative CDR1 contact
regions show improved recognition in B6 mice. The rank order of recognition is
different using the P14 transgenic T cells, suggesting that one reason for
improved recognition is a change in the TCR repertoire that recognizes the
peptide. However, the affinity of the TCR by some of the peptide/MHC complex
with increased recognition is improved, as shown by increased tetramer binding
to P14 T cells. These substitutions at the termini of the peptide-binding cleft
cause localized conformational changes as seen by changes in mAb binding and
crystallographic structures. The different peptide structures also show
different conformations in the center of the peptide, but these are shown to be
energetically similar and thus most likely have no significance with respect to
TCR recognition. Therefore, small conformational changes, localized to the CDR1
contact regions, may play a significant role in TCR recognition.
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Secondary reference #1
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Title
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Structural evidence of t cell xeno-Reactivity in the absence of molecular mimicry.
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Authors
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R.Zhao,
D.J.Loftus,
E.Appella,
E.J.Collins.
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Ref.
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J Exp Med, 1999,
189,
359-370.
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PubMed id
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