Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR-H1-derived peptide CB1.
A systematic exploration of the V(H)2/V(kappa)12-13 variable domains of the anti-CD4 monoclonal antibody (mAb) 13B8.2 was performed by the Spot method to screen for paratope-derived peptides (PDPs) demonstrating CD4 binding ability. Nine peptides, named CB1 to CB9, were identified, synthesized in a cyclic and soluble form and tested for binding to recombinant soluble CD4. Among them, CB1, CB2 and CB8 showed high anti-CD4 activity. Competition studies for CD4 binding indicated that PDPs CB1, CB8, and the parental mAb 13B8.2 recognized the same complementarity determining region (CDR)3-like loop region. PDP CB1 was shown to mimic the biological properties of 13B8.2 mAb in two independent cellular assays, demonstrating inhibitory activities in the micromolar range on antigen presentation and human immunodeficiency virus promoter activation. Our results indicate that the bioactive CDR-H1 PDP CB1 has retained a significant part of the parental 13B8.2 mAb properties and might be a lead for the design of anti-CD4 peptidomimetics of clinical interest.
Bès
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C
CNRS-UMR 5094, Faculté de Pharmacie, Institut de Biotechnologie et Pharmacologie, 15 avenue Charles Flahault, 34060 Montpellier Cedex 2, France.
Briant-Longuet
L
L
Cerruti
M
M
De Berardinis
P
P
Devauchelle
G
G
Devaux
C
C
Granier
C
C
Chardès
T
T
DeBerardinis
P
P
D000818:Animals; D019380:Anti-HIV Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D017951:Antigen Presentation; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism
C110023:13B8-2 monoclonal antibody; D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins