RESTRICTED TCR V-ALPHA GENE REARRANGEMENTS IN T-CELLS RECOGNIZING AN IMMUNODOMINANT PEPTIDE OF MYELIN BASIC-PROTEIN IN DR2 PATIENTS WITH MULTIPLE-SCLEROSIS

T cell responses to myelin basic protein (MBP) are thought to play an important role in the pathogenesis of multiple sclerosis (MS). The res ponse to the 83-99 region of MBP represents a dominant response to MBP in patients with MS and is associated with HLA-DRS that is linked wit h susceptibility to MS. Although T cell clones reactive to various reg ions of MBP have been found to exhibit heterogeneous TCR V-beta gene u sage in patients with MS, it is unclear whether T cell clones uniforml y recognizing the 83-99 peptide of MBP in the context of the same DR m olecule would have restricted TCR V gene rearrangements and recognitio n motifs, In this study, a panel of DR2- or DR4-restricted T cell clon es specific for the MBP83-99 peptide were derived from 11 patients wit h MS and examined for TCR V gene usage by PCR and the recognition moti fs using analog peptides, Our study revealed that despite a few T cell clone pairs having similar recognition motifs and shared sequence hom ology in the CDR3, the overall recognition motifs of MBP83-99-specific T cells were considerably diverse. Interestingly, the DRS-restricted T cell crones displayed a biased V gene usage for V(alpha)3 and V(alph a)8, while V-beta gene rearrangements were highly heterogeneous. This study provided experimental evidence suggesting a limited heterogeneit y in TCR V, gene rearrangements of MBP-reactive T cells in DR2 patient s with MS.