CLONAL EXPANSION OF T-CELL RECEPTOR-BETA GENE SEGMENT IN THE RETROCOCHLEAR LESIONS OF EAE MICE

It has been reported that the T cell receptor V beta 8.2 (TcrbV8.2) ge ne segment is predominantly expressed in encephalomyelitic T cells res ponding to myelin basic protein (MBP) in experimental allergic encepha lomyelitis (EAE) mice, We have demonstrated retrocochlear hearing loss in EAE mice in previous studies. Administration of a monoclonal antib ody specific to the T cell receptor V beta 8 (TcrbV8) subfamily preven ted both this type of hearing loss and the central nerve disease. In t his study, we examined the role of the TcrbV8.2 gene segment in the re trocochlear lesions of EAE mice. A clonal expression of T cell recepto r beta chain gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) was identified in the retrocochlear lesions. The TcrbV8.2 gene segment appears to recom bine only with TcrbJ2.1 (32.1%) and TcrbJ2.7 (67.9%) gene segments, Th e TcrbJ2,7 gene segment has also been previously identified as the dom inant TcrbJ gene in the lymph nodes of EAE mice. Only TcrbD2, with a l ength of 4 amino acids, was observed recombining with these TcrbV8.2 s equences, G and C nucleotides are predominantly expressed at the N reg ions between the V-D and D-J junctions. This dominant TcrbV gene segme nt (TcrbV8.2-TcrbD2-TcrbJ2.7) observed in the retrocochlear lesions ha s been identified in the MBP-specific T cells from the lymph nodes of EAE mice. These results suggest that a small subset of antigen-specifi c T cells migrate to, and expand at, the retrocochlear lesions, which leads to hearing loss.