Covalent binding of C3b to monoclonal antibodies selectively up-regulates heavy chain epitope recognition by T cells
✍ Scribed by Lyse Santoro; Christian Drouet; Angeline Reboul; Jean-Pierre Mach; Maurice G. Colomb
- Book ID
- 102824321
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 768 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Covalent binding of C3b to monoclonal antibodies selectively up-regulates heavy chain epitope recognition by T cells
Protein C3 of the complement system is known for its role in the nonspecific immune response. Covalent binding of C3b to antigen upon complement activation also plays a significant role in specific Tcell immune response. C3b-antigen complexes can bind to complement receptors on the antigenpresenting cell, and the C3b antigen link (most often an ester link) remains fairly stable inside the cells. In this study, IgG1,x and IgG2a,x murine monoclonal antibodies (mAb) were used as antigens; covalent complexes between mAb and C3b were produced and purified in vitro from purified proteins; human B cell lines and Tcell clones were raised from tumor patients who received mAb injections for cancer therapy or diagnosis. Recognition of epitopes of these mAb by Tcell clones when the mAb were processed alone or bound to C3b was compared. IgG or IgG-C3b complexes presented by Bcell lines were able to stimulate proliferation of x light chain-specific Tcell clones at similar concentrations. In contrast, IgG-C3b complex recognition by heavy chain-specific T cell clones required 100-fold less IgG-C3b than uncomplexed IgG. As C3b was shown to be covalently bound only to the IgG heavy chains in the complexes, C3b chaperoning is restricted to only the IgG heavy chain and selectively influences intracellular steps of IgG heavy chain processing. This differential modulation of C3b suggests an early dissociation of IgG heavy and light chains in antigenpresenting cells.