A recombinant human scFv anti-Rh(D) antibody with multiple valences using a C-terminal fragment of C4-binding protein.
Monomeric recombinant molecules prove generally unsatisfactory for in vivo use. Most biological systems are indeed multivalent either structurally, associating different chains, or functionally, when cross-linked by their ligands. Mimicking natural molecules for immune intervention implies the need for multimerizing systems to create multivalent molecules capable of interfering with physiological processing. A multivalent anti-Rh(D) recombinant protein has been designed by reconstructing the antibody binding site of a human monoclonal anti-Rh(D) antibody as a single chain Fv mini antibody, then multimerizing it by inserting at its C-terminal end the C-terminal part of the C4 binding protein (C4bp) alpha chain, which is responsible for the octamer multimerization of that molecule. This soluble multivalent recombinant molecule was functional, bound red blood cells (RBCs), agglutinated them, and did not activate complement. This demonstration model opens the way for future in vivo use of multivalent molecules associating antibody valences and other functional molecules for cell targeting, imaging, or removal of cells such as Rh(D)-positive RBCs for preventing Rh alloimmunization.
Libyh
M T
MT
Laboratoire d'Immunologie, UFR Médecine, Pôle Biomolécules URCA, Reims, France.
Goossens
D
D
Oudin
S
S
Gupta
N
N
Dervillez
X
X
Juszczak
G
G
Cornillet
P
P
Bougy
F
F
Reveil
B
B
Philbert
F
F
Tabary
T
T
Klatzmann
D
D
Rouger
P
P
Cohen
J H
JH
D000595:Amino Acid Sequence; D018033:Antibodies, Bispecific / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D003181:Complement C4 / Q000276:immunology; D006801:Humans; D016167:Integrin alphaXbeta2; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003181:Complement C4; D016167:Integrin alphaXbeta2; D011994:Recombinant Proteins; D012204:Rh-Hr Blood-Group System