A common TCR V-D-J sequence in V beta 13.1 T cells recognizing an immunodominant peptide of myelin basic protein in multiple sclerosis

T cell responses to the immunodominant peptide (residues 83-99) of myelin b asic protein are potentially associated with multiple sclerosis (MS), This study was undertaken to examine whether a common sequence motif(s) exists w ithin the TCR complemintarity-determining region (CDR)-3 of T cells recogni zing the MBP83-99 peptide. Twenty MBP83-99-reactive T cell clones derived f rom patients with MS were analyzed for CDR3 sequences, which revealed sever al shared moths, Some V beta 13.1 T cell clones derived from different pati ents with MS were Found to contain an identical CDR3 motif, V beta 13.1-LGR AGLTY. Oligonucleotides complementary to the shared CDR3 moths were used as specific probes to detect identical target CDR3 sequences in a large panel of T cell lines reactive to MBP83-99 and unprimed PBMC, The results reveal ed that, in contrast to other CDRS moths examined, the LGRAGLTY motif was c ommon to T cells recognizing the MBP83-99 peptide, as evident by its expres sion in the majority of MBP83-99-reactive T cell lines (36/44) and PBMC spe cimens (15/48) obtained from randomly selected MS patients. The motif was a lso detected in lower expression in some PBMC specimens from healthy indivi duals, suggesting the presence of low precursor frequency of T cells expres sing this motif in healthy individuals. This study provides new evidence in dicating that the identified LGRAGLTY motif is preferentially expressed in MBP83-99-reactive T cells. The findings have important implications in moni toring and targeting MBP83-99-reactive T cells in MSI.