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

作者：Smolarek Dorota; Hattab Claude; Hassanzadeh Ghassabeh Gholamreza; Cochet Sylvie; Gutierrez Carlos; de Brevern Alexandre G; Udomsangpetch Rachanee; Picot Julien; Grodecka Magdalena; Wasniowska Kazimiera; Muyldermans Serge; Colin Yves; Le Van Kim Caroline; Czerwinski Marcin; Bertrand Olivier^*

来源：Cellular and Molecular Life Sciences, 2010, 67(19): 3371-3387.

DOI：10.1007/s00018-010-0387-6

• Duffy antigen receptor for chemokines
• VHH
• Atypical chemokine receptor
• Plasmodium vivax
• Immunoaffinity
• Cancer
• Inflammation
• HIV

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.

• 出版日期2010-10