Fine T cell receptor repertoire analysis of spinal cord T cells responding to the major and minor epitopes of myelin basic protein during rat autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis is a disease induced by neuroantigen‐reactive T cells bearing particular types of T cell receptor (TCR). Although the nature of TCRs of encephalitogenic T cells has been partially delineated using encephalitogenic T cell clones established in vitro, the entire TCR repertoire formed in situ after immunization with neuroantigen remains unclear. In the present study, we immunized Lewis rats with myelin basic protein (MBP) and its fragment peptides and determined the TCR repertoire of spinal cord T cells formed after the immunization by CDR3 spectratyping. It was revealed that the oligoclonal expansion of Vβ2, Vβ8.2, and Vβ17 spectratypes was detectable after immunization with guinea pig MBP and its immunodominant epitope, the 68–88 sequence, whereas immunization with a peptide containing a minor epitope induced Vβ10 expansion. Immunization with rat MBP induced much broader TCR Vβ expansion (all of the above Vβs plus Vβ3). These findings suggest that TCRs activated by immunization with guinea pig MBP used as heteroclitic immunogen recognize autoantigen, rat MBP. Furthermore, the strategy used in this study gives insight into the pathogenesis of autoimmune disease and provides useful information for designing TCR‐based immunotherapy. J. Neurosci. Res. 59:145–152, 2000 © 2000 Wiley‐Liss, Inc.