Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation.
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.
Zhang
X
X
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104-6082, USA.
Piatier-Tonneau
D
D
Auffray
C
C
Murali
R
R
Mahapatra
A
A
Zhang
F
F
Maier
C C
CC
Saragovi
H
H
Greene
M I
MI
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
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments