Related Experiment Videos
MRL/Mp-lpr/lpr mouse derived monoclonal antibodies that recognise determinants shared by poly (ADP-ribose), single
Abstract:
MRL/Mp-lpr/lpr (MRL/l) mice spontaneously produce antibodies to poly(ADP-ribose) that are cross-reactive with single stranded DNA (ssDNA). Spleen cells from these animals were used for fusion with murine plasmacytoma cells to prepare hybridomas that produce autoantibodies to poly(ADP-ribose). Monoclonal antibodies (MoAb) produced by the selected hybridomas not only preferred ssDNA to poly(ADP-ribose), but also reacted with left handed Z-DNA; the MoAb reflected the nature of serum antibodies to poly (ADP-ribose) in MRL/l mice. These results suggest that similar antigenic determinants exist in poly (ADP-ribose), ssDNA and left handed Z-DNA and that the cross-reactive nature of autoantibodies to poly (ADP-ribose) in MRL/l mice may be the results of expansion of such clones as selected in this experiment.
Insights
Mice with lupus (MRL/l) produce autoantibodies that target poly(ADP-ribose) and single-stranded DNA (ssDNA). Hybridoma technology confirmed these autoantibodies also bind Z-DNA, suggesting shared molecular structures.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- MRL/Mp-lpr/lpr (MRL/l) mice are a model for autoimmune diseases.
- These mice spontaneously develop autoantibodies against poly(ADP-ribose).
- These autoantibodies cross-react with single-stranded DNA (ssDNA).
Purpose of the Study:
- To generate hybridomas producing monoclonal antibodies (MoAb) against poly(ADP-ribose).
- To characterize the reactivity of these MoAb.
- To investigate the antigenic determinants shared between poly(ADP-ribose), ssDNA, and Z-DNA.
Main Methods:
- Spleen cells from MRL/l mice were fused with murine plasmacytoma cells.
- Hybridomas producing autoantibodies to poly(ADP-ribose) were selected.
- Monoclonal antibodies were tested for reactivity against poly(ADP-ribose), ssDNA, and Z-DNA.
Main Results:
- Selected monoclonal antibodies showed a preference for ssDNA over poly(ADP-ribose).
- The monoclonal antibodies also reacted with left-handed Z-DNA.
- The reactivity profile of the monoclonal antibodies mirrored that of serum autoantibodies in MRL/l mice.
Conclusions:
- Shared antigenic determinants likely exist among poly(ADP-ribose), ssDNA, and Z-DNA.
- The cross-reactivity of autoantibodies in MRL/l mice may result from the expansion of clones recognizing these shared structures.