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Journal ArticleDOI

Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis.

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TLDR
This is the first report demonstrating the use of a synthetic T CR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.
Abstract
T CELLS expressing the αβ T-cell receptor (TCR) for antigen can elicit anti-idiotypic antibodies specific for the TCR that regulate T-cell function1–4. Defined sequences of the TCR, however, have not been used to elicit specific antibodies and the role of cellular immunity directed against TCR determinants has not been studied. We immunized Lewis rats with a synthetic peptide representing a hypervariable region of the TCR β8 molecule. Subsequent induction of experimental autoimmune encephalomyelitis, a paralytic disease of the central nervous system mediated primarily by Vβ8+ T cells specific for myelin basic protein5,6 was prevented. T cells specific for the TCR Vβ8 peptide conferred passive protection against the disease to naive rats, apparently by shifting the predominant T-cell response away from the major encephalitogenic epitope of basic protein. This is the first report demonstrating the use of a synthetic TCR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.

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Citations
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Journal ArticleDOI

Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen.

TL;DR: In mice with chronic EAE, several additional determinants of MBP in peptides 35–47, 81–100 and 121–140 recall proliferative responses and reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1–11 alone, demonstrating priming by endogenous MBP determinants.
Journal ArticleDOI

Immunological aspects of demyelinating diseases

TL;DR: Recent research in MS has been focused on the characterization of cellular immune responses against myelin components and the results of these studies are reviewed and the potential implications for the pathogenesis and future therapy of MS are examined.
Journal ArticleDOI

Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.

TL;DR: Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide in a subgroup of patients, which raise important considerations for the use of specific immunotherapies in general.
Journal ArticleDOI

Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor.

TL;DR: It is found that nonstimulatory analogs of the HA peptide preferentially inhibit HA-specific T cells in inhibition of antigen presentation assays, which results in antigen-specific competitive blocking of T cell responses by virtue of their capacity to compete with DR1-antigen complexes for binding to the T cell receptor.
Journal ArticleDOI

Autoimmune diseases: the failure of self tolerance

TL;DR: The induction of autoimmunity involves genetic and environmental factors that have focused the attention of researchers on the trimolecular complex formed by major histocompatibility complex molecules, antigen, and T cell receptors, points to potential strategies for disease intervention.
References
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Journal ArticleDOI

T-cell antigen receptor genes and T-cell recognition.

TL;DR: This view of T-cell recognition has implications for how the receptors might be selected in the thymus and how they (and immunoglobulins) may have arisen during evolution.
Journal ArticleDOI

Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex

TL;DR: The presence of Mlsa/ MHC during T-cell development results in the deletion of T cells that express Vβ8.1, documenting the importance of clonal deletion in establishing tolerance to self antigens.
Journal ArticleDOI

Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention

TL;DR: Prevention and reversal of autoimmune disease with V beta 8-specific monoclonal antibodies was achieved in EAE because of a striking similarity in fine specificity of T cell receptors.
Journal ArticleDOI

T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens.

TL;DR: T lymphocytes reactive with the product of the Mlsa-allele of the minor lymphocyte stimulating (Mls) locus use a predominant T-cell receptor β-chain variable gene segment (Vβ6), consistent with a model in which tolerance to self antigens is achieved by clonal deletion.
Journal ArticleDOI

A sequence pattern common to T cell epitopes.

TL;DR: An analysis of the known cytotoxic and helper T cell epitopes has revealed similarity within their primary sequences, arguing that the binding of peptide antigens to class I and class II is similar in nature.
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