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From the Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts 02115
The frequency of clonally expanded and persistent T cells recognizing the immunodominant
autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in
subjects with typical relapsing remitting multiple sclerosis (MS). T cells expressing mRNA
transcripts encoding T cell receptor (TCR)-
and -
chains found in T cell clones previously
isolated from these subjects recognizing the MBPp85-99 epitope were examined. In contrast to
frequencies of 1 in 105-106 as measured by limiting dilution analysis, estimates of the T cell frequencies expressing MBPp85-99-associated TCR chain transcripts were as high as 1 in 300. These high frequencies were confirmed by performing PCR on single T cells isolated by flow
cytometry. MBPp85-99 TCR transcripts were present in IL-2 receptor -positive T cells
which were induced to undergo Fas-mediated cell death upon antigen stimulation. These data
demonstrate that at least a subpopulation of patients with MS can have a very high frequency of
activated autoreactive T cells.
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