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) gene segment is predominantly expressed in encephalomyelitic T cells responding to myelin basic protein (MBP) in experimental allergic encephalomyelitis (EAE) mice. We have demonstrated retrocochlear hearing loss in EAE mice in previous studies. Administration of a monoclonal antibody specific to the T cell receptor V beta 8 (TcrbV8) subfamily prevented both this type of hearing loss and the central nerve disease. In this study, we examined the role of the TcrbV8.2 gene segment in the retrocochlear lesions of EAE mice. A clonal expression of T cell receptor beta chain gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) was identified in the retrocochlear lesions. The TcrbV8.2 gene segment appears to recombine only with TcrbJ2.1 (32.1%) and TcrbJ2.7 (67.9%) gene segments. The TcrbJ2.7 gene segment has also been previously identified as the dominant TcrbJ gene in the lymph nodes of EAE mice. Only TcrbD2, with a length of 4 amino acids, was observed recombining with these TcrbV8.2 sequences. G and C nucleotides are predominantly expressed at the N regions between the V-D and D-J junctions. This dominant TcrbV gene segment (TcrbV8.2-TcrbD2-TcrbJ2.7) observed in the retrocochlear lesions has been identified in the MBP-specific T cells from the lymph nodes of EAE mice. These results suggest that a small subset of antigen-specific T cells migrate to, and expand at, the retrocochlear lesions, which leads to hearing loss.
Cheng
K C
KC
Department of Medicine, University of Tennessee, Memphis 38163, USA.
Lee
K M
KM
Yoo
T J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003051:Cochlea / Q000473:pathology; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D004676:Myelin Basic Protein / Q000276:immunology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta