Journal ArticleDOI
T cell unresponsiveness correlates with quantitative TCR levels in a transgenic model.
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TLDR
Findings support the notion that there is a definable quantitative signal threshold which is critical for tolerance induction.Abstract:
Two lines of transgenic mice were developed which differ in their level of expression of V beta 11. To determine the role of TCR density in tolerance induction, these mice were bred with I-E expressing mice and were investigated for tolerance induction. T cells expressing V beta 11 at high density are deleted by negative selection. T cells expressing < 10% of the normal TCR receptor density are not subject to negative selection and were not activated in vitro. There is a correlation in receptor density in both strains of mice with in vitro activation. These findings support the notion that there is a definable quantitative signal threshold which is critical for tolerance induction.read more
Citations
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Journal ArticleDOI
Low avidity recognition of self-antigen by T cells permits escape from central tolerance
George Y. Liu,Paul J. Fairchild,Richard M. Smith,John R. Prowle,Dimitris Kioussis,David C. Wraith +5 more
TL;DR: This work has addressed the hypothesis that the avidity of T cell recognition in the thymus may be compromised, enabling autoreactive T cells to escape self-tolerance by constructing transgenic mice expressing an encephalitogenic T cell receptor (TCR) by using analogs of intermediate affinity.
Journal ArticleDOI
Impact of Negative Selection on the T Cell Repertoire Reactive to a Self-Peptide: A Large Fraction of T Cell Clones Escapes Clonal Deletion
TL;DR: It is suggested that numerous low-affinity self-specific T cells persist in the periphery and shown that a deleting ligand can specifically narrow the structural diversity of the TCR repertoire.
Book ChapterDOI
T Lymphocyte Tolerance: From Thymic Deletion to Peripheral Control Mechanisms
TL;DR: This chapter discusses the central and peripheral tolerance in the T-cell population and self-tolerance in the B- cell population and the understanding of tolerance induction in lymphocyte subpopulations is exponentially advanced in the generation of T- and B-cell receptor transgenic mice.
Journal ArticleDOI
Limited capacity for tolerization of CD4+ T cells specific for a pancreatic β cell neo-antigen
Irmgard Förster,Irmgard Förster,Ryutaro Hirose,Jeffrey M. Arbellt,Björn E. Clausen,Douglas Hanahant +5 more
TL;DR: Tolerization of CD4+ T cells specific for a rare self-antigen may fail if too many autoreactive T cells develop, as seen in crossbred mice in which transgenic T cells comprised a majority of the T cell population were nontolerant.
Journal ArticleDOI
T-cell tolerance and autoimmunity in transgenic models of central and peripheral tolerance
TL;DR: The value of the transgenic approach is that it can overcome the low frequency of peptide-specific T cells occurring in normal animals, and also provide a tissue-specific, cognate antigen that is absent in controls.
References
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Journal ArticleDOI
Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens.
TL;DR: This paper used hybridoma monoclonal antibodies obtained after immunization of mice with rat cells to study rat cell-surface antigens present on subpopulations of rat lymphocytes.
Journal ArticleDOI
The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides
Alain Townsend,Jonathan B. Rothbard,Frances M. Gotch,G. Bahadur,David C. Wraith,Andrew J. McMichael +5 more
TL;DR: The authors showed that the epitopes of nucleoprotein recognized by CTL in association with class I molecules of the major histocompatibility complex in both mouse and man can be defined with short synthetic peptides derived from the nucleopprotein sequence.
Journal ArticleDOI
Identification of a monoclonal antibody specific for a murine T3 polypeptide
TL;DR: Results identify T3-epsilon as a cell surface protein involved in the transduction of activation signals and can both activate and inhibit T-cell function.
Journal ArticleDOI
Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.
Pamela S. Ohashi,Stephan Oehen,Kurt Buerki,Hanspeter Pircher,Cara T. Ohashi,Bernhard Odermatt,Bernard Malissen,Rolf M. Zinkernagel,Hans Hengartner +8 more
TL;DR: This model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation, in so-called "T cell-mediated autoimmune diseases".
Journal ArticleDOI
Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: Role of anti-self (virus) immune response
TL;DR: The results indicate that a viral gene introduced as early as an animal's egg stage, incorporated into the germline, and expressed in islet cells does not produce tolerance when the host is exposed to the same virus later in life.