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The immunological synapse during T c...

Richie, Lauren Ilyse.

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The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta./
Author:	Richie, Lauren Ilyse.
Description:	151 p.
Notes:	Adviser: Mark M. Davis.
Contained By:	Dissertation Abstracts International63-05B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3048669
ISBN:	0493687521

The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta.
Richie, Lauren Ilyse.

The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta. - 151 p.

Adviser: Mark M. Davis.

Thesis (Ph.D.)--Stanford University, 2002.

*This dissertation includes a CD that is compound (contains both a paper copy and a CD as part of the dissertation). The CD requires the following application: QuickTime Movie Player.

ISBN: 0493687521Subjects--Topical Terms:

1017734
Biology, Microbiology.

The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta.
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008 110425s2002 eng d
020 $a 0493687521
035 $a (UnM)AAI3048669
035 $a AAI3048669
040 $a UnM $c UnM
100 1 $a Richie, Lauren Ilyse. $3 1251286
245 1 0 $a The immunological synapse during T cell maturation and activation: Imaging the translocation ofp56lck and CD3zeta.
300 $a 151 p.
500 $a Adviser: Mark M. Davis.
500 $a Source: Dissertation Abstracts International, Volume: 63-05, Section: B, page: 2195.
502 $a Thesis (Ph.D.)--Stanford University, 2002.
520 $a *This dissertation includes a CD that is compound (contains both a paper copy and a CD as part of the dissertation). The CD requires the following application: QuickTime Movie Player.
520 $a T cell receptor (TCR) ligation can induce different signals resulting in cell fates ranging from activation to apoptosis. For example, thymic positive selection promotes maturation of self-major histocompatibility complex (MHC)-restricted thymocytes, while negative selection, results in apoptosis of autoreactive thymocytes. In mature T cells, agonists induce proliferation, while antagonists block activation. Since all of these signals are transmitted via the TCR, associated CD3 chains, co-receptors, and tyrosine kinases, it is unclear how T cells initiate different signaling cascades. The immunological synapse is an ordered accumulation of proteins at the T cell: antigen presenting cell (APC) interface; perhaps differences in synapse architecture might contribute to alternate signaling cascades. To address this hypothesis, we utilized high-speed time-lapse fluorescent microscopy to observe immunological synapse formation downstream of these different TCR stimuli in real time. Green fluorescent protein (GFP) fusions of lck and CD3ζ were expressed in thymocytes and in mature T cells. Transduced thymocytes were imaged in reaggregate cultures as they interacted with thymic stroma that induced positive or negative selection. Similarly, transduced T cell blasts were imaged as they interacted with agonist or antagonist-pulsed APCs. Three-dimensional reconstructions of the cells were generated and rotated to view the immunological synapse <italic>en face </italic>. We observed that negatively selecting stroma induced efficient thymocyte conjugate formation and rapid accumulation of lck and CD3ζ to the synapse periphery. In contrast, positively selecting stroma failed to induce efficient conjugate formation. During mature T cell activation lck accumulated at the synapse periphery, while CD3ζ accumulated in the center of the synapse. This suggests that peripheral CD3ζ accumulations might contribute to apoptotic signals, while central accumulations might contribute to activation. Furthermore, the majority of lck co-localized with CD4 at the synapse periphery and was only briefly in proximity to CD3ζ early in synapse formation, suggesting a limited window of opportunity for efficient lck-mediated CD3 phosphorylations. Antagonist peptides failed to induce efficient conjugate formation or lck accumulations. Finally, an intracellular pool of lck was recruited to the immunological synapse following agonist but not antagonist stimulation. These data provide evidence that differential immunological synapse architecture reflects the nature of TCR-mediated signals.*
590 $a School code: 0212.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0410
690 $a 0982
710 2 0 $a Stanford University. $3 754827
773 0 $t Dissertation Abstracts International $g 63-05B.
790 $a 0212
790 1 0 $a Davis, Mark M., $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3048669