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

TitleA recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines.
Publication TypeJournal Article
Year of Publication2010
AuthorsSmolarek, D., C. Hattab, G. Hassanzadeh-Ghassabeh, S. Cochet, C. GutiƩrrez, A. G. de Brevern, R. Udomsangpetch, J. Picot, M. Grodecka, K. Wasniowska, S. Muyldermans, Y. Colin, C. Le Van Kim, M. Czerwinski, and O. Bertrand
JournalCell Mol Life Sci
Volume67
Issue19
Pagination3371-87
Date Published2010 Oct
ISSN1420-9071
KeywordsAnimals, Blood Group Antigens, Camels, Carrier Proteins, Chemokines, Duffy Blood-Group System, Erythrocytes, Humans, Immunoglobulins, Interleukin-8, Plasmodium vivax, Receptors, Antigen, Receptors, Cell Surface, Receptors, Chemokine, Recombinant Proteins
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.

DOI10.1007/s00018-010-0387-6
Alternate JournalCell. Mol. Life Sci.
PubMed ID20458517
PubMed Central IDPMC2966875