The specific aim of this proposal is to dissect the T-cell receptor (TCR) repertoire of autoimmune ear disease (AED). We will test if the following hypotheses will apply. 1. T-cells are the key factors in mediating AED and therefore AED can be transferrable by cell transfer to naive syngeneic mice. 2. TCR usage in mice is restricted so that limited numbers of Valpha and Vbeta gene segments are used in AED. 3. If such specific TCR V segment usage in AED is identified, therapies using either antibodies against these TCRs or peptides from Vbeta CDR2 sequence may be used to abrogate the small population of T-cells that can cause AED. To investigate the above specific aims, we will (1) produce a series of ear disease inducing T-cell lines and T-cell hybridomas (made from disease inducing T-cell) specific to collagen and peptides (epitope containing). (2) We will determine the DNA structures of the TCR gene and TCR gene usage in ear tissue will also be examined. (3) Antibodies will be used to block these TCRs. (4) Also, peptides of the GDR2 region of Valpha and Vbeta will be synthesized to inhibit the T-cell response to antigen in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC000652-04A3
Application #
2125873
Study Section
Hearing Research Study Section (HAR)
Project Start
1989-08-01
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Internal Medicine/Medicine
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

Showing the most recent 10 out of 14 publications