Our hypothesis is that audiovestibular manifestation in relapsing polychondritis (RP) is caused by autoimmunity to specific epitope(s) on cyanogen bromide-11 (CB-11) peptide of type II collagen (CII). This may be tested by inducing ear lesions (auricular chondritis, eustachian tube chondritis, cochlear vasculitis) with monoclonal antibodies specific for these epitope(s). The long term objective of this proposal is to understand the basic pathogenic mechanisms of audiovestibular manifestation of relapsing polychondritis and a collagen autoimmunity in hearing loss. The specific approach of this proposal is to dissect the antibody repertoire, of mice which react with peptides obtained from CB-11 of CII and identify similar antibodies to type II collagen in human patients with relapsing polychondritis associated with hearing loss. 1. Develop a panel of monoclonal antibodies (Mab) specific for CB-11 peptide fragments of type II collagen obtained by cyanogen bromide (CBO digestion. 2. Identify the epitopic specificity of each Mab for small peptides obtained by isolation proteolytic fragments of CB-cleaved peptide (CB-11). 3. Induce collagen-induced ear disease with monoclonal antibodies with epitopes specificity of CB-11 peptide in mice. 4. Synthesize the chondriti inducing epitopic structure in CB-11 fragments and produce ear lesions in mice with these peptides. 5. Determine if antibodies from patients with relapsing polychondritis bind epitopes identified as important in the mouse model and to the synthetic ear lesions inducing peptide. Mice will be given monoclonal antibodies to induce ear disease. After finding ear disease inducing epitope, these peptides will also be made and ear disease will be induced by these synthetic peptides. Sera from RP with ear disease will be tested for the epitope specificity of these peptides and ear disease inducing epitope will be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC000652-01
Application #
3217267
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Kwon, Soon Seog; Kim, Nachsung; Yoo, Tae-June (2005) The effects of intradermal vaccination with DNA encoding for the T-cell receptor on the induction of experimental autoimmune encephalomyelitis in B10.PL mice. J Korean Med Sci 20:1039-45
Du, Xiaoping; Mora, Renzo; Barbieri, Marco et al. (2003) TUNEL-positive labeling in mouse inner ear caused by tubulin immunization is not apoptosis. ORL J Otorhinolaryngol Relat Spec 65:17-21
Matsuoka, Hiroshi; Kwon, Soon Seog; Yazawa, Yoshiro et al. (2002) Induction of endolymphatic hydrops by directly infused monoclonal antibody against type II collagen CB11 peptide. Ann Otol Rhinol Laryngol 111:587-92
Kim, N; Cheng, K C; Kwon, S S et al. (2001) Oral administration of collagen conjugated with cholera toxin induces tolerance to type II collagen and suppresses chondritis in an animal model of autoimmune ear disease. Ann Otol Rhinol Laryngol 110:646-54
Cheng, K C; Matsuoka, H; Lee, K M et al. (2000) Proto-oncogene Raf-1 as an autoantigen in Meniere's disease. Ann Otol Rhinol Laryngol 109:1093-8
Matsuoka, H; Cheng, K C; Krug, M S et al. (1999) Murine model of autoimmune hearing loss induced by myelin protein P0. Ann Otol Rhinol Laryngol 108:255-64
Suzuki, M; Cheng, K C; Krug, M S et al. (1998) Successful prevention of retrocochlear hearing loss in murine experimental allergic encephalomyelitis with T cell receptor Vbeta8-specific antibody. Ann Otol Rhinol Laryngol 107:917-27
Cheng, K C; Lee, K M; Yoo, T J (1998) Clonal expansion of T-cell receptor beta gene segment in the retrocochlear lesions of EAE mice. ORL J Otorhinolaryngol Relat Spec 60:126-32
Yoo, T J; Fujiyoshi, T; Cheng, K C et al. (1997) Molecular basis of type II collagen autoimmune ear diseases. Ann N Y Acad Sci 830:221-35
Suzuki, M; Cheng, K C; Matsuoka, H et al. (1997) The cochlear protein antigens 28 kd and 30 kd, and their antibodies in Meniere's disease. Ann N Y Acad Sci 830:211-20

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