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A peptide that antagonizes tcr-mediated reactions with both syngeneic and allogeneic agonists: Functional and structural aspects

Academic Article
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Overview

authors

  • Rudolph, M. G.
  • Shen, L. Q.
  • Lamontagne, S. A.
  • Luz, J. G.
  • Delaney, J. R.
  • Ge, Q.
  • Cho, B. K.
  • Palliser, D.
  • McKinley, C. A.
  • Chen, J. Z.
  • Wilson, Ian
  • Eisen, H. N.

publication date

  • March 2004

journal

  • Journal of Immunology  Journal

abstract

  • We identify and consider some characteristics of a peptide antagonist for the Ag-specific receptor on 2C cells (the 2C TCR). The peptide, GNYSFYAL (called GNY), binds to H-2K(b), and a very high-resolution crystal structure of the GNY-K(b) complex at 1.35 A is described. Although the GNY peptide does not bind to L(d), the potency of GNY-K(b) as an antagonist is evident from its ability to specifically inhibit 2C TCR-mediated reactions to an allogenic agonist complex (QLSPFPFDL-L(d)), as well as to a syngeneic agonist complex (SIYRYYGL-K(b)). The crystal structure and the activities of alanine-substituted peptide variants point to the properties of the peptide P4 side chain and the conformation of the Tyr-P6 side chain as the structural determinants of GNYSFYAL antagonist activity.

subject areas

  • Alanine
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Arginine
  • Cell Line
  • Cell Line, Tumor
  • Clone Cells
  • Crystallography, X-Ray
  • Cytotoxicity Tests, Immunologic
  • Female
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Isoantigens
  • Lysine
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligopeptides
  • Protein Binding
  • Receptors, Antigen, T-Cell
  • Serine
  • Structure-Activity Relationship
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 14978103
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Additional Document Info

start page

  • 2994

end page

  • 3002

volume

  • 172

issue

  • 5

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