TCR REPERTOIRE TO PROTEOLIPID PROTEIN (PLP) IN MULTIPLE-SCLEROSIS (MS) - HOMOLOGIES BETWEEN PLP-SPECIFIC T-CELLS AND MS-ASSOCIATED T-CELLS IN TCR JUNCTIONAL SEQUENCES

In the pathogenesis of multiple sclerosis (MS), autoimmune T cells rea ctive with proteolipid protein (PLP) may play a crucial role, We deter mined 23 TCR beta-chain sequences of limiting dilution T cell lines (T CL) selected against a synthetic peptide, PLP 95-116, 105-124 or 139-1 55, from the peripheral blood of three Japanese MS patients with the D R2,w15 haplotype (TI, SK and OK). Fourteen sequences were originated f rom TI, seven from SK and two from OK. The PLP-reactive TCL utilized v arious V-beta and J(beta) gene segments, but there was significant bia s in the V-beta and J(beta) usage, Overutilization of the V(beta)2 fam ily and dominant usage of the J(beta)2,5 subfamily was seen in PLP 105 -124-reactive and 95-116-reactive TCL respectively, More remarkably, a majority of the TCL were found to express beta-chain CDR3 motifs that appear to be unique to MS brain infiltrates, In contrast, these motif s were only rarely seen in control TCR sequences from peripheral blood or from a TCL selected against tetanus toroid, In several cases, the beta CDR3 homologies between the PLP-reactive T cells and MS brain T c ells were extensive, owing to the shared motifs in combination with th e surrounding amino acid identities, These results indicate that PLP-s pecific T cells may be involved in the immunopathology of MS.