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

To characterize the nature of the or chain of TCR associated with the devel opment of experimental autoimmune encephalomyelitis (EAE), spinal cord T ce lls isolated from individual rats with preclinical and clinical EAE were in vestigated by CDR3 spectratyping and subsequently, the amino acid sequences of the CDR3 region of oligoclonally expanded TCR determined. In contrast t o the beta chain repertoire in which V beta 8.2 with the shortest CDR3 is t he predominant population throughout the course, multiple oligoclonal expan sion was observed at all time points examined. Characteristically, V alpha 1 and V alpha 2 expansion was observed at preclinical and early stages, whe reas that of V alpha 8, V alpha 13 and V alpha 23 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 la tter group had the KLTF motif in the C terminal region of CDR3. These findi ngs suggest that V alpha 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. (C) 1999 Elsevier Science B.V. All rights reserved.