ANALYSIS OF V-BETA-8-CDR3 SEQUENCES DERIVED FROM CENTRAL-NERVOUS-SYSTEM OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

We have recently demonstrated that a strong bias for expression of V b eta 8.2 is manifested early during the onset of experimental autoimmun e encephalomyelitis (EAE) induced by guinea pig basic protein (Gp-BP) immunization of Lewis rats. More importantly, the V beta 8.2 bias was observed in T cells infiltrating the spinal cord (SC) and in cerebrosp inal fluid (CSF), but was not present in T cells isolated from the per iphery. Here, we report the V beta 8-CDR3 sequences found in unselecte d SC, CSF, and lymph node (LN) T cell populations at onset of Gp-BP-in duced EAE. Striking similarities were observed among sequences derived from SC and CSF. Evidence for oligoclonal expansion of V beta 8.2 seq uences associated with previously characterized encephalitogenic clone s was observed in both SC and CSF, but not in LN. An AspSer CDR3 motif identified in encephalitogenic clones recognizing the dominant 72-89 epitope of Gp-BP was found in 9/22 SC cDNA clones, 11/24 CSF cDNA clon es, and 1/16 LN cDNA clones. Interestingly, J beta 2.7 and J beta 1.3 were also highly represented in SC and CSF, but not in LN. Given that these sequences were derived from T cells present at the site of autoi mmune attack and not selected by in vitro manipulation, the data offer compelling evidence that 1) selective recruitment and/or expansion of V beta 8.2(+) T cells are occurring in the central nervous system; 2) these events are at least partially dependent on V beta residues whic h are likely to influence Ag binding; and 3) CSF-derived T cells provi de a representative view of CNS events at the onset of EAE.