Selection for T-cell receptor Vβ-Dβ-Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis

Jorge R. Oksenberg, Michael A. Panzara, Ann B. Begovich, Dennis Mitchell, Henry A. Erlich, Ronald S. Murray, Richard Shimonkevitz, Martina Sherritt, Jonathan Rothbard, Claude C.A. Bernard, Lawrence Steinman

Research output: Contribution to journalArticleResearchpeer-review

395 Citations (Scopus)

Abstract

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 Vβ5.2 genes were detected in the brains of all patients who were HLA DRB1*1501, DQA1*0102, DQB1 *0602, DPB1*0401. The Vβ5.2-Dβ- Jβ 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 Vβ5.2 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 Vβ5.2 N(D)N rearrangements in MS lesions. The capacity of rat T cells with these VDJ sequences to cause experimental allergic encephalomyelitis2 and the prevalence of such sequences in demyelinated human lesions indicate that T cells with this rearranged TCR may be critical in MS.

Original languageEnglish
Pages (from-to)68-70
Number of pages3
JournalNature
Volume362
Issue number6415
DOIs
Publication statusPublished - 1993
Externally publishedYes

Cite this

Oksenberg, J. R., Panzara, M. A., Begovich, A. B., Mitchell, D., Erlich, H. A., Murray, R. S., Shimonkevitz, R., Sherritt, M., Rothbard, J., Bernard, C. C. A., & Steinman, L. (1993). Selection for T-cell receptor Vβ-Dβ-Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature, 362(6415), 68-70. https://doi.org/10.1038/362068a0