Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis

Nature. 1993 Mar 4;362(6415):68-70. doi: 10.1038/362068a0.


Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which a restricted cellular immune response has been observed. In order to establish whether such T cell responses are likely to be antigen-specific particularly with regard to myelin basic protein (MBP), we analysed T-cell receptor (TCR) gene rearrangements directly from MS brain plaques, using the polymerase chain reaction on reverse transcribed messenger RNA, and compared these with TCR of previously described MBP-specific T cell clones from MS and the rat model experimental allergic encephalomyelitis. Rearranged V beta 5.2 genes were detected in the brains of all patients who were HLA DRB1*1501, DQA1*0102, DQB1*0602, DPB1*0401. The V beta 5.2-D beta-J beta sequences in these MS brain plaques revealed five motifs. One of the common motifs was identical to that described for the VDJ region of a V beta 5.2 T-cell clone. This clone was from an MS patient who was HLA DRB1*1501, DQB1*0602, DPB1*0401, and it was cytotoxic towards targets containing the MBP peptide 89-106 (ref. 1). The deduced amino-acid sequence of this VDJ rearrangement, Leu-Arg-Gly, has also been described in rat T cells cloned from experimental allergic encephalomyelitis lesions, which are specific for MBP peptide 87-99 (ref. 2). VDJ sequences with specificity for this MBP epitope constitute a large fraction (40%) of the TCR V beta 5.2 N(D)N rearrangements in MS lesions. The capacity of rat T cells with these VDJ sequences to cause experimental allergic encephalomyelitis and the prevalence of such sequences in demyelinated human lesions indicate that T cells with this rearranged TCR may be critical in MS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / immunology*
  • Brain / pathology
  • CD3 Complex / genetics*
  • Cloning, Molecular
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • HLA-D Antigens / analysis
  • HLA-D Antigens / genetics*
  • Humans
  • Molecular Sequence Data
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Myelin Basic Protein / immunology*
  • Oligodeoxyribonucleotides
  • Phenotype
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / genetics
  • Rats
  • Spinal Cord / immunology
  • T-Lymphocytes / immunology


  • CD3 Complex
  • HLA-D Antigens
  • Myelin Basic Protein
  • Oligodeoxyribonucleotides
  • RNA, Messenger