Alexandre G. de Brevern's publications

Year 2010

  1. Smolarek D., Hattab C., Hassanzadeh-Ghassabeh G., Cochet S., Gutiérrez C.,
    de Brevern A.G., Udomsangpetch R., Picot J., Grodecka M., Wasniowska K.,
    Muyldermans S., Colin Y., Le Van Kim C., Czerwinski M., Bertrand O.
    A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy Antigen Receptor for Chemokines
    Cellular and Molecular Life Sciences (2010) in press.

    The Fy blood group antigens are carried by the Duffy Antigen Receptor for Chemokines (DARC), a receptor for Plasmodium vivax, playing a role in cancer progression, inflammation and possibly implicated in HIV infection. We immunized a dromedary against the N-terminal extracellular domain of DARC. Recombinant VHHs, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from the dromedary lymphocytes and selected for DARC binding. The described VHH, CA52 does recognize native DARC on cells by agglutination and flow cytometry. CA52 inhibits P. vivax invasion of red blood cells and displaces interleukin-8 bound to Fy-positive cells. The targeted epitope overlaps the well defined Fy6 epitope involved in parasite and chemokines binding. The equilibrium dissociation constant of CA52 and the recombinant N-terminal extracellular domain of DARC is sub-nanomolar and ideal to develop diagnostic or therapeutic compounds. The immunocapture by immobilized CA52 and elution with peptide epitope yielded highly purified DARC from engineered K562 cells. This first report on the identification of a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify and to modulate the function of cellular markers.

Alexandre G. de Brevern
Last Modification : March 2024
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