Restricted TCR Valpha 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 animportant role in the pathogenesis of multiple sclerosis (MS). The responseto the 83-99 region of MBP represents a dominant response to MBP inpatients with MS and is associated with HLA-DR2 that is linked withsusceptibility to MS. Although T cell clones reactive to various regions ofMBP have been found to exhibit heterogeneous TCR Vbeta gene usage inpatients with MS, it is unclear whether T cell clones uniformly recognizingthe 83-99 peptide of MBP in the context of the same DR molecule would haverestricted TCR V gene rearrangements and recognition motifs. In this study,a panel of DR2- or DR4-restricted T cell clones specific for the MBP83-99peptide were derived from 11 patients with MS and examined for TCR V geneusage by PCR and the recognition motifs using analog peptides. Our studyrevealed that despite a few T cell clone pairs having similar recognitionmotifs and shared sequence homology in the CDR3, the overall recognitionmotifs of MBP83-99-specific T cells were considerably diverse.Interestingly, the DR2-restricted T cell clones displayed a biased V geneusage for Valpha3 and Valpha8, while Vbeta gene rearrangements were highlyheterogeneous. This study provided experimental evidence suggesting alimited heterogeneity in TCR Valpha gene rearrangements of MBP-reactive Tcells in DR2 patients with MS.