SYNTHETIC CD4 EXOCYCLIC PEPTIDES ANTAGONIZE CD4 HOLORECEPTOR BINDING AND T-CELL ACTIVATION

We have developed peptide analogs to analyze precise human CD4 substru ctures involved in MHC class II binding. Forms of the complementarity determining-like regions (CDRs) of the D1 domain of human CD4 were rep roduced 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 c reate a heteromeric CD4 complex, blocked IL-2 production and antagoniz ed the normal function of the CD4 receptor. The approach of creating n ovel synthetic antagonistic receptor complexes may represent a new rec eptor specific pharmaceutical approach to modulate biological function .