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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / metabolism
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Amino Acid Sequence
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Amino Acid Substitution / immunology
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Animals
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Arginine / metabolism
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Cell Line
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Cell Line, Tumor
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Clone Cells
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Crystallography, X-Ray
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Cytotoxicity Tests, Immunologic
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Female
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H-2 Antigens / metabolism
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Histocompatibility Antigen H-2D
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Isoantigens / physiology*
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Lysine / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Oligopeptides / chemistry*
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Oligopeptides / metabolism
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Oligopeptides / physiology*
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / agonists
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Receptors, Antigen, T-Cell / antagonists & inhibitors*
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Receptors, Antigen, T-Cell / physiology*
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Serine / metabolism
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Structure-Activity Relationship
Substances
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigen H-2D
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Isoantigens
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Oligopeptides
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Receptors, Antigen, T-Cell
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Serine
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Arginine
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Lysine
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Alanine