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

Experimental autoimmune encephalomyelitis is a disease induced by neuroanti gen-reactive T cells bearing particular types of T cell receptor (TCR). Alt hough the nature of TCRs of encephalitogenic T cells has been partially del ineated using encephalitogenic T cell clones established in vitro, the enti re TCR repertoire formed in situ after immunization with neuroantigen remai ns 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 spectra-typing . It was revealed that the oligoclonal expansion of V beta 2, V beta 8.2, a nd V beta 17 spectratypes was detectable after immunization with guinea pig MBP and its immunodominant epitope, the 68-88 sequence, whereas immunizati on with a peptide containing a minor epitope induced V beta 10 expansion. I mmunization with rat MBP induced much broader TCR VP expansion (all of the above V beta s plus V beta 3). These findings suggest that TCRs activated b y immunization with guinea pig MBP used as heteroclitic immunogen recognize autoantigen, rat MBP. Furthermore, the strategy used in this study gives i nsight into the pathogenesis of autoimmune disease and provides useful info rmation for designing TCR-based immunotherapy. (C) 2000 Wiley-Liss, Inc.