A Peptide That Antagonizes TCR-Mediated Reactions with Both Syngeneic and Allogeneic Agonists: Functional and Structural Aspects

Markus G. Rudolph, Lucy Q. Shen, Stephen A. Lamontagne, John G. Luz, Joseph R. Delaney, Qing Ge, Bryan K. Cho, Deborah Palliser, Carol A. McKinley, Jianzhu Chen, Ian A. Wilson, Herman N. Eisen

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13 Scopus citations

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 H2Kb, and a very high-resolution crystal structure of the GNY-Kb complex at 1.35 Å is described. Although the GNY peptide does not bind to Ld, the potency of GNY-Kb as an antagonist is evident from its ability to specifically inhibit 2C TCR-mediated reactions to an allogenic agonist complex (QLSPFPFDL-Ld), as well as to a syngeneic agonist complex (SIYRYYGL-Kb). 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 GNYS FYAL antagonist activity.

Original languageEnglish (US)
Pages (from-to)2994-3002
Number of pages9
JournalJournal of Immunology
Volume172
Issue number5
DOIs
StatePublished - Mar 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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., Wilson, I. A., & Eisen, H. N. (2004). A Peptide That Antagonizes TCR-Mediated Reactions with Both Syngeneic and Allogeneic Agonists: Functional and Structural Aspects. Journal of Immunology, 172(5), 2994-3002. https://doi.org/10.4049/jimmunol.172.5.2994