title: Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104-6082, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Piatier-Tonneau
authors.forename: C
authors.initials: C
authors.lastname: Auffray
authors.forename: R
authors.initials: R
authors.lastname: Murali
authors.forename: A
authors.initials: A
authors.lastname: Mahapatra
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: C C
authors.initials: CC
authors.lastname: Maier
authors.forename: H
authors.initials: H
authors.lastname: Saragovi
authors.forename: M I
authors.initials: MI
authors.lastname: Greene
mesh_terms: D000595:Amino Acid Sequence; D001709:Biotechnology; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments