Project Details
Description
The immune idiotype:anti-idiotype (Id:anti-Id) network is important in
immunoregulation and tolerance. Its analysis in experimental autoimmune
myasthenia gravis (EAMG) should provide insight into the abnormal
immunoregulation in a defined antibody-mediated autoimmune disease, We have
produced isogeneic monoclonal anti-Id antibodies directed against
EAMG-inducing anti-acetylcholine receptor (AChR) monoclonal antibodies
(mAbs) to be used as tools to analyze the immune network in EAMG. We have
purified and characterized five anti-Id mAbs directed against two of these
anti-AChR mAbs. Immunochemical analysis reveals that these anti-Ids are
noncompetitive inhibitors of antigen (Ag) (i.e., ACHR) binding to the
anti-AChR mabs. The Ids defined by the anti-Ids are moderately crossreactive with other
anti-AChR mabs and with EAMG sera without being present in dominant levels.
We have, nonetheless, suppressed the total serum anti-AChR antibody levels
and prevented the development of EAMG by pretreating animals, prior to
immunization with AChR, with physiologic doses of individual anti-Id mAb.
These anti-Id thus play a major immunoregulatory role in EAMG. In our
present proposal, the aim is to analyze the mechanism(s) involved in this
observed suppression of the total anti-AChR response induced by
manipulating an Id that is moderately crossreactive but not dominant in
EAMG sera. Experiments are proposed to: a) further analyze the parameters
important to the development of suppression (animal age, Ag dose, adjuvants
used, and dose and timing of anti-Id) in order to characterize this
biological system and to maximize the suppression; b) analyze the
structural and cellular mechanisms involved in the observed suppression. To
analyze structural mechanisms at a molecular level, we will clone and
sequence the variable regions of the anti-AChR mAb 132A and the
corresponding anti-Id-mAb HC-4A. To analyze cellular mechanisms, altered B
cell secretions of Ab by anti-Id, and the role of specific B cell
populations (Id + and anti-Id +) will be determined. This analysis of the
immune network in EAMG should have implications for the understanding and
treatment of human MG and other autoimmune diseases.
immunoregulation and tolerance. Its analysis in experimental autoimmune
myasthenia gravis (EAMG) should provide insight into the abnormal
immunoregulation in a defined antibody-mediated autoimmune disease, We have
produced isogeneic monoclonal anti-Id antibodies directed against
EAMG-inducing anti-acetylcholine receptor (AChR) monoclonal antibodies
(mAbs) to be used as tools to analyze the immune network in EAMG. We have
purified and characterized five anti-Id mAbs directed against two of these
anti-AChR mAbs. Immunochemical analysis reveals that these anti-Ids are
noncompetitive inhibitors of antigen (Ag) (i.e., ACHR) binding to the
anti-AChR mabs. The Ids defined by the anti-Ids are moderately crossreactive with other
anti-AChR mabs and with EAMG sera without being present in dominant levels.
We have, nonetheless, suppressed the total serum anti-AChR antibody levels
and prevented the development of EAMG by pretreating animals, prior to
immunization with AChR, with physiologic doses of individual anti-Id mAb.
These anti-Id thus play a major immunoregulatory role in EAMG. In our
present proposal, the aim is to analyze the mechanism(s) involved in this
observed suppression of the total anti-AChR response induced by
manipulating an Id that is moderately crossreactive but not dominant in
EAMG sera. Experiments are proposed to: a) further analyze the parameters
important to the development of suppression (animal age, Ag dose, adjuvants
used, and dose and timing of anti-Id) in order to characterize this
biological system and to maximize the suppression; b) analyze the
structural and cellular mechanisms involved in the observed suppression. To
analyze structural mechanisms at a molecular level, we will clone and
sequence the variable regions of the anti-AChR mAb 132A and the
corresponding anti-Id-mAb HC-4A. To analyze cellular mechanisms, altered B
cell secretions of Ab by anti-Id, and the role of specific B cell
populations (Id + and anti-Id +) will be determined. This analysis of the
immune network in EAMG should have implications for the understanding and
treatment of human MG and other autoimmune diseases.
| Status | Finished |
|---|---|
| Effective start/end date | 9/20/90 → 8/31/94 |
Funding
- National Institutes of Health
- National Institutes of Health
- National Institutes of Health: $70,189.00
ASJC
- Medicine(all)
- Neuroscience(all)