In C57BL/6 (B6) mice, the T cell response to acetylcholine receptor from Torpedo callfomlca (TAChR) provides a specific antibody response and symptoms of muscular weakness similar to those displayed in the human disease myasthenia gravis. We had found previously that the B6 T cell response to AChR shows limited clonaltty, both in terms of the epltopes recognized and in terms of the diversity of the TCR Vβ gene segments used. We now report that all TAChR-reactlve B6 T cell clones which responded to the dominant antigenlc epltope and expressed the dominant TCR Vβ6 gene segment exhibited conservation of amlno acid sequence in the VDJ junctional region (CDR3) of the TCR β chain. The conserved sequence motif contained a glutamlc acid residue in the CDR3 of TCR β. Analysis of TCR β sequences from antigen-primed lymph node cells (LNC) showed a similar enrichment for sequences having a glutamlc acid in CDR3, although the overall appearance of the LNC sequences was somewhat more heterogeneous and consistent with a gradual In vitro selection of the subset of TCR found in the T cell clones. As the first example of TCR sequences in this model of myasthenia gravis, these results begin to provide a context for understanding self-non-self discrimination of AChR. In particular, the unusually conserved CDR3 sequence suggests that the conserved Vβ gene utilization seen previously is directly related to recognition of the immunodominant peptlde epltope in association with the experimental autoimmune myasthenia gravls-susceptlbllity determining MHC class II molecule I-Ab.
- Experimental autoimmune myasthenia gravis
- V-D-J junction
ASJC Scopus subject areas
- Immunology and Allergy