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

J Immunol. 2004 Mar 1;172(5):2994-3002. doi: 10.4049/jimmunol.172.5.2994.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine / metabolism
  • Amino Acid Sequence
  • Amino Acid Substitution / immunology
  • Animals
  • Arginine / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Clone Cells
  • Crystallography, X-Ray
  • Cytotoxicity Tests, Immunologic
  • Female
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Isoantigens / physiology*
  • Lysine / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism
  • Oligopeptides / physiology*
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell / physiology*
  • Serine / metabolism
  • Structure-Activity Relationship


  • H-2 Antigens
  • H-2Kb protein, mouse
  • Histocompatibility Antigen H-2D
  • Isoantigens
  • Oligopeptides
  • Receptors, Antigen, T-Cell
  • Serine
  • Arginine
  • Lysine
  • Alanine

Associated data

  • PDB/1LK2