T cell epitopes in experimental autoimmune myasthenia gravis of the rat: strain‐specific epitopes and cross‐reaction between two distinct segments of the α chain of the nicotinic acetylcholine receptor (torpedo californica)

Zhang, Yiping; Barkas, T.; Juillerat, Marcel A.; Schwendimann, Bernard; Wekerle, Hartmut

doi:10.1002/eji.1830180410

Cited by 34 publications

(9 citation statements)

References 36 publications

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“…In Lewis rats, tAChR a subunit region 100-116 [21], comprising 97-112 [22], contains the major immunodominant T cell epitope of tAChR, which is recognized by CD4' T cells in a MHC RT1.BL-restricted manner [22]. To investigate whether the inhibition of EAMG was due to blockade of the immunodominant RT1.BL-restricted T cell response, we evaluated whether the tAChR97-112 specific T cell response was decreased.…”

Section: Discussionmentioning

confidence: 99%

“…The major T cell epitope involved in tAChR-induced EAMG in Lewis rats is the 97-112 sequence of the a subunit of tAChR [21, 221. This epitope is recognized by specific CD4' T cells in OO14-2980/96/1212-2866$10.00 + .25IO a MHC class I1 RT1.BL-restricted fashion [22]. We show here that co-immunization of a strong RT1.BL-binding ovalbumin peptide (OVA323-339) along with tAChR efficiently inhibited EAMG induction.…”

Section: Introductionmentioning

confidence: 86%

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Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response

et al. 1996

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To assess the capacity of major histocompatibility complex (MHC) class II-binding competitor peptides in inhibiting antibody-mediated disease processes, we studied experimental autoimmune myasthenia gravis in Lewis rats. Experimental autoimmune myasthenia gravis, a disease model mediated by T cell-dependent autoantibodies against acetylcholine receptors, was induced by immunization with Torpedo californica acetylcholine receptor emulsified in complete Freund's adjuvant. The immunodominant acetylcholine receptor T cell epitope was recognized by T cells in the context of MHC class II RT1.B(L). The disease inhibitory capacity of RT1.B(L)-binding peptides not related to the acetylcholine receptor was determined upon co-immunization with Torpedo acetylcholine receptor. Co-immunization of peptide OVA323-339, a strong RT1.B(L)-binding competitor peptide, resulted in complete disease inhibition. Although, the priming of the anti-acetylcholine receptor T cell response was not fully inhibited, the kinetics of the response was changed. Moreover, besides a drastic reduction of the anti-Torpedo acetylcholine receptor antibody titers, a shift in isotype distribution was found. These findings indicate that antibody-mediated autoimmune processes can be suppressed by MHC class II competitor peptides. Furthermore, the administration of such peptides in vivo not only passively inhibits T cell activation, but also functionally alters the immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response

et al. 1996

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“…In another autoimmune disease, myasthenia gravis, the main immunogenic region for T cells and antibody responses is in close proximity on the acetylcholine receptor, the pathogenic autoantigen in this condition (29). Whether neighboring or overlapping T-and B-cell epitopes is a general feature of autoimmunity warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Fine specificity of the antibody response to myelin basic protein in the central nervous system in multiple sclerosis: the minimal B-cell epitope and a model of its features.

Warren

Catz²,

Steinman³

1995

Proc. Natl. Acad. Sci. U.S.A.

102

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“…An immunodominant epitope, Ta100-116, has been identified and, as in the mouse, recognition of the epitope appears to correlate with strain susceptibility [62,63]. T cells reactive with this epitope are able to provide help for a diverse population of B cells [64].…”

Section: Alternative Rodent Models Of Eamgmentioning

confidence: 99%

Myasthenia Gravis and its Animal Model: T Cell Receptor Expression in an Antibody Mediated Autoimmune Disease

Infante

Kraig²

1999

International Reviews of Immunology

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Myasthenia gravis (MG) is a prototypic antibody-mediated autoimmune disease. Since the primary target antigen of the autoimmune response is known and a well-characterized animal model is available, MG is often considered an excellent situation for the application of novel specific immunotherapies, many of which are directed at T lymphocytes. CD4+ helper T cells are required for the development of the animal model, experimental autoimmune MG (EAMG). Even though the target antigen, acetylcholine receptor (AChR) is immunologically complex, the T cell response to AChR in mice is dominated by recognition of a single peptide by about 50% of the T cells. These T cells, in turn, utilize a restricted set of TCR gene elements and conserved CDR3 regions. While specific therapy directed at the immunodominant T cells is capable of reducing the magnitude of the anti-AChR response, considerable flexibility is apparent and reveals the ability of additional T cells to provide the requisite B cell help. In human MG patients, AChR-specific T cells have been identified but in many studies the frequencies were surprisingly low. In a very few cases, AChR-specific T cells have been cloned from MG patients. Analysis reveals heterogeneity in epitope recognition and MHC restriction. Little information on TCR structure is available. Our own studies using antigen-specific as well as non-specific methods for examining clonal T cell expansions in MG have led to an alternative hypothesis concerning T-B collaboration in MG.

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T cell epitopes in experimental autoimmune myasthenia gravis of the rat: strain‐specific epitopes and cross‐reaction between two distinct segments of the α chain of the nicotinic acetylcholine receptor (torpedo californica)

Cited by 34 publications

References 36 publications

Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response

Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response

Fine specificity of the antibody response to myelin basic protein in the central nervous system in multiple sclerosis: the minimal B-cell epitope and a model of its features.

Myasthenia Gravis and its Animal Model: T Cell Receptor Expression in an Antibody Mediated Autoimmune Disease

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