International Immunology, Vol 10, 97-106, Copyright © 1998 by Oxford University Press
E Munoz, L Vidarte, MT Casado, C Pastor and F Vivanco
The covalent binding of C3 to antigen-antibody complexes [immune complexes
(IC)] plays a pivotal role in the elimination of antigens. C3 prevents the
formation of large IC lattices promoting their solubilization.
Subsequently, bound C3 fragments determine the efficacy of antigen
presentation, and the generation of antibody responses and immunological
memory. C3 binding to IgG-IC generates IgG-C3b-C3b complexes which are
detected by SDS-PAGE as two major bands: C3alpha65- heavy chain and
C3alpha65-C3alpha43 covalent complexes. Using human heat-aggregated IgG1 as
a model of IC, a C3b binding site was localized only in the Cgamma1 domain.
However, with true IC of ovalbumin and rabbit IgG anti-ovalbumin, C3b binds
to both the Fab and Fc regions of IgG. To study the binding of C3b to the
different domains of IgG and particularly to evaluate the involvement of
the Cgamma1 domain, we have constructed recombinant single-chain antibodies
without Cgamma1, which have the structure:
V(H)-linker-V(L)-hinge-Cgamma2-Cgamma3 (scAb). The variable domains were
from a mouse mAb anti-HSA and the constant region (hinge-C(H)2-C(H)3) from
human IgG1 or rabbit IgG. C3 binds very efficiently to IC formed with human
(h-scAb) or rabbit (r-scAb) recombinant antibodies (scAb-HSA) and generates
also two bands on SDS- PAGE (C3alpha65-scAb and C3alpha65-C3alpha43), which
are the counterparts of those of the complete antibody. In addition, IC
formed with scAb activate the alternative pathway to a similar extent as IC
of the entire IgG. These data indicate that the Cgamma1 domain is a
dispensable region for C3b binding and that the remaining constant domains
are as efficient as Cgamma1 in C3b binding. Overall these results support
the view that C3 does not specifically recognize a unique site in the
Cgamma1 domain. Rather it seems to be able to attach along the antibody
molecule. Probably this implies an advantage for effective processing of
C3b-IC and elimination of antigens in vivo.
ARTICLES
The C(H)1 domain of IgG is not essential for C3 covalent binding: importance of the other constant domains as targets for C3
Department of Immunology, Fundacion Jimenez Diaz, Madrid, Spain.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Jelezarova, A. Luginbuehl, and H. U. Lutz C3b2-IgG Complexes Retain Dimeric C3 Fragments at All Levels of Inactivation J. Biol. Chem., December 19, 2003; 278(51): 51806 - 51812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-G. Hu, A. Z. Alvi, D. Chau, J. E. Coles, R. E. Fulton, M. R. Suresh, and L. P. Nagata Development and Characterization of a Novel Fusion Protein Composed of a Human IgG1 Heavy Chain Constant Region and a Single-Chain Fragment Variable Antibody against Venezuelan Equine Encephalitis Virus J. Biochem., January 1, 2003; 133(1): 59 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Vidarte, C. Pastor, S. Mas, A. B. Blazquez, V. de los Rios, R. Guerrero, and F. Vivanco Serine 132 Is the C3 Covalent Attachment Point on the CH1 Domain of Human IgG1 J. Biol. Chem., October 5, 2001; 276(41): 38217 - 38223. [Abstract] [Full Text] [PDF]
|
|