Literature DB >> 20458517

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines.

Dorota Smolarek1, Claude Hattab, Gholamreza Hassanzadeh-Ghassabeh, Sylvie Cochet, Carlos Gutiérrez, Alexandre G de Brevern, Rachanee Udomsangpetch, Julien Picot, Magdalena Grodecka, Kazimiera Wasniowska, Serge Muyldermans, Yves Colin, Caroline Le Van Kim, Marcin Czerwinski, Olivier Bertrand.   

Abstract

Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on 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.

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Year:  2010        PMID: 20458517      PMCID: PMC2966875          DOI: 10.1007/s00018-010-0387-6

Source DB:  PubMed          Journal:  Cell Mol Life Sci        ISSN: 1420-682X            Impact factor:   9.261


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