Stage-dependent usage of TCR alpha chains with different CDR3 motifs by spinal cord T cells in autoimmune...

To characterize the nature of the alpha chain of TCR associated with the development of experimental autoimmune encephalomyelitis (EAE), spinal cord T cells isolated from individual rats with preclinical and clinical EAE were investigated by CDR3 spectratyping and subsequently, the amino acid sequences of the CDR3 region of oligoclonally expanded TCR determined. In contrast to the beta chain repertoire in which Vbeta8.2 with the shortest CDR3 is the predominant population throughout the course, multiple oligoclonal expansion was observed at all time points examined. Characteristically, Valpha1 and Valpha2 expansion was observed at preclinical and early stages, whereas that of Valpha8, Valpha13 and Valpha23 was detected at early and peak stages. Sequence analysis of the CDR3 region revealed that the former group possessed an asparagine repeat in the middle portion, whereas the latter group had the KLTF motif in the C terminal region of CDR3. These findings suggest that Valpha usage by EAE-associated T cells is stage-dependent and that EAE is induced by polyclonally activated T cells which switch TCR alpha chain, but not beta chain, phenotype as the disease progresses.