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Updated: Aug 11, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation
X Zhang1, D Piatier-Tonneau, C Auffray
1Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104-6082, USA.
Abstract:
We have developed peptide analogs to analyze precise human CD4 substructures involved in MHC class II binding. Forms of the complementarity determining-like regions (CDRs) of the D1 domain of human CD4 were reproduced as synthetic aromatically modified exocyclic (AME) analogs and tested for their ability to block CD4-MHC II interactions and T cell activation. The exocyclic derived from CDR3 (residues 82-89) of human CD4, which specifically associated with CD4 on the T cell surface to create a heteromeric CD4 complex, blocked IL-2 production and antagonized the normal function of the CD4 receptor. The approach of creating novel synthetic antagonistic receptor complexes may represent a new receptor specific pharmaceutical approach to modulate biological function.
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