Restricted TCR Valpha gene rearrangements in T cells recognizing an immunodominant peptide of myelin basic protein in DR2 patients with multiple sclerosis |
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Authors: | Zang YC; Kozovska M; Aebischer I; Li S; Boehme S; Crowe P; Rivera VM; Zhang JZ |
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Affiliation: | Department of Neurology and Baylor-Methodist International Multiple Sclerosis Center, Baylor College of Medicine, Veterans Affairs Medical Center, Houston, TX 77030, USA. |
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Abstract: | T cell responses to myelin basic protein (MBP) are thought to play an
important role in the pathogenesis of multiple sclerosis (MS). The response
to the 83-99 region of MBP represents a dominant response to MBP in
patients with MS and is associated with HLA-DR2 that is linked with
susceptibility to MS. Although T cell clones reactive to various regions of
MBP have been found to exhibit heterogeneous TCR Vbeta gene usage in
patients with MS, it is unclear whether T cell clones uniformly recognizing
the 83-99 peptide of MBP in the context of the same DR molecule would have
restricted TCR V gene rearrangements and recognition motifs. In this study,
a panel of DR2- or DR4-restricted T cell clones specific for the MBP83-99
peptide were derived from 11 patients with MS and examined for TCR V gene
usage by PCR and the recognition motifs using analog peptides. Our study
revealed that despite a few T cell clone pairs having similar recognition
motifs and shared sequence homology in the CDR3, the overall recognition
motifs of MBP83-99-specific T cells were considerably diverse.
Interestingly, the DR2-restricted T cell clones displayed a biased V gene
usage for Valpha3 and Valpha8, while Vbeta gene rearrangements were highly
heterogeneous. This study provided experimental evidence suggesting a
limited heterogeneity in TCR Valpha gene rearrangements of MBP-reactive T
cells in DR2 patients with MS.
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