TCR usage in human and experimental demyelinating disease

Hafler, David A.; Saadeh, Mark; Kuchroo, Vijay K.; Milford, Edgar L.; Steinman, Lawrence

doi:10.1016/0167-5699(96)80611-6

Cited by 101 publications

(57 citation statements)

References 60 publications

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“…Our results parallel the observations in B10.PL and PL/J mice (I-A u haplotype) and in the Lewis rat, in which the encephalitogenic response is restricted with respect to epitope specificity and TCR usage (68). On the other hand, they contrast the paradigm of other previously characterized MBP T cell epitopes that bind with high affinity to the MHC and show a more diverse TCR usage, both in humans (45,69,70) and in the SJL/J (I-A s haplotype) mouse (Martin, R., personal …”

Section: Discussionsupporting

confidence: 58%

Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.

et al. 1997

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Section: Discussionsupporting

confidence: 58%

Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.

et al. 1997

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“…The identification of clonal restriction in the TCR repertoire of infiltrating T cells has been of keen interest to immunologists (10,(37)(38)(39). Such a restriction in the TCRs may provide a powerful tool to control T cells involved in autoimmune responses by specifically eliminating the TCR-bearing T cell populations (10,11).…”

Section: Discussionmentioning

confidence: 99%

Clonal Expansion of Infiltrating T Cells in the Spinal Cords of SJL/J Mice Infected with Theiler’s Virus

Kang

Mohindru

Kang

et al. 2000

The Journal of Immunology

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Intracerebral infection of susceptible mice with Theiler’s murine encephalomyelitis virus results in immune-mediated inflammatory demyelination in the white matter and consequent clinical symptoms. This system has been utilized as an important virus model for human multiple sclerosis. Although the potential involvement of virus-specific Th cells has been studied extensively, very little is known about the nature of T cells infiltrating the CNS during viral infection and their role in the development of demyelinating disease. In this study, the clonal nature of T cells in the spinal cord during the disease course was analyzed using size spectratyping and sequencing of the TCR β-chain CDR3 region. These studies clearly indicate that T cells are clonally expanded in the CNS after viral infection, although the overall TCR repertoire appears to be diverse. The clonal expansion appears to be Ag-driven in that it includes Th cells specific for known viral epitopes. Interestingly, such restricted accumulation of T cells was not detectable in the infiltrates of mice with proteolipid protein peptide-induced experimental autoimmune encephalomyelitis. The initial T cell repertoire (7–9 days postinfection) seems to be more diverse than that observed in the later stage (65 days) of virally induced demyelination, despite the more restricted utilization of Vβ subfamilies. These results strongly suggest continuous stimulation and clonal expansion of virus-specific T cells in the CNS of Theiler’s murine encephalomyelitis virus-infected mice during the entire course of demyelinating disease.

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“…TCR analysis in patients with tissue-specific autoimmune diseases such as rheumatoid arthritis or multiple sclerosis have shown variation in immunodominant clonotypes among individuals, and within the targeted tissues (i.e., joints or brain plaques) of the same individual (29,30). Interestingly, Carnaud and colleagues (31) have also demonstrated that a high degree of heterogeneity of TCR CDR3␤ gene usage exists at an early age among islets in NOD mice, although the specificity of these T cells was not determined.…”

Section: Discussionmentioning

confidence: 99%

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

Wong

Stevens

Long

et al. 2007

The Journal of Immunology

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A major issue regarding T cell responses in autoimmunity is how the repertoire compares between the periphery and target organ. In type 1 diabetes, the status of at-risk or diabetic individuals can be monitored by measuring β cell-specific T cells isolated from PBL, but whether these T cells accurately reflect the repertoire residing in the pancreatic islets is unclear. The TCR repertoire of disease-relevant, tetramer-sorted CD8+ T cells was examined at the single-cell level in PBL, pancreatic lymph nodes (PLN), and the islets of individual NOD mice. CDR3α and CDR3β sequences demonstrated that the same repertoire of T cells in PBL was detected in the islets and PLN, although the frequency of specific clonotypes varied. Albeit infrequent, clonotypes that were prevalent in the islets but not found in PBL were also detected. β cell Ag immunization expanded immunodominant PBL clonotypes present in the islets and PLN. These results show that insight into repertoire profiles of islet-infiltrating T cells can be obtained from PBL.

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TCR usage in human and experimental demyelinating disease

Cited by 101 publications

References 60 publications

Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.

Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.

Clonal Expansion of Infiltrating T Cells in the Spinal Cords of SJL/J Mice Infected with Theiler’s Virus

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

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