Restricted TCR Valpha gene rearrangements in T cells recognizing an immunodominant peptide of myelin basic protein in DR2 patients with multiple sclerosis.
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.
Department of Neurology and Baylor-Methodist International Multiple Sclerosis Center, Baylor College of Medicine, Veterans Affairs Medical Center, Houston, TX 77030, USA.
Y C
YC
Zang
M
M
Kozovska
I
I
Aebischer
S
S
Li
S
S
Boehme
P
P
Crowe
V M
VM
Rivera
J Z
JZ
Zhang
D000595:Amino Acid Sequence; D004247:DNA / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D015802:HLA-DR2 Antigen; D016056:Immunodominant Epitopes; D007135:Immunoglobulin Variable Region; D004676:Myelin Basic Protein; D004247:DNA