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Activation induced T cell membrane r...

Fahmy, Tarek M.

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Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen./
作者:	Fahmy, Tarek M.
面頁冊數:	192 p.
附註:	Adviser: Jonathan P. Schneck.
Contained By:	Dissertation Abstracts International62-10B.
標題:	Biophysics, General. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3028263
ISBN:	0493403140

Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen.
Fahmy, Tarek M.

Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen. - 192 p.

Adviser: Jonathan P. Schneck.

Thesis (Ph.D.)--The Johns Hopkins University, 2002.

Control of the dynamic range of physiological responses is a central biological process. In the T cell immune response, physiologic states of activation are associated with changes in the dynamic range of responsiveness. Thus, cells which have never encountered antigen, naive T cells, require high levels of antigen to proliferate and differentiate into activated T cells. While activated T cells can respond to low doses of antigen

ISBN: 0493403140Subjects--Topical Terms:

1019105
Biophysics, General.

Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen.
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245 1 0 $a Activation induced T cell membrane reorganization: A mechanism for sensing low density of antigen.
300 $a 192 p.
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500 $a Source: Dissertation Abstracts International, Volume: 62-10, Section: B, page: 4452.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2002.
520 $a Control of the dynamic range of physiological responses is a central biological process. In the T cell immune response, physiologic states of activation are associated with changes in the dynamic range of responsiveness. Thus, cells which have never encountered antigen, naive T cells, require high levels of antigen to proliferate and differentiate into activated T cells. While activated T cells can respond to low doses of antigen
520 $a While studies have indicated a role for TCR clustering in effector functions, there has been no analysis of whether T cell receptor organization and subsequent changes in the TCR avidity are modulated in different physiologic states. Here we examined the influence of activation on the ability of T cells to bind dimeric peptide MHC complexes. We use dimeric complexes as an idealized representation of an antigen presenting cell. Using these complexes in a fluorescence based binding assay, we found that increased binding of peptide/MHC dimers to activated T cells compared to naive cells was apparent at both 4°C and 37°C. The TCR, on activated T cells, was readily crosslinked by soluble dimeric MHC I molecules, increasing the overall binding affinity (avidity) of the TCR for peptide-MHC complex.
520 $a The increased number of crosslinks observed on activated T cells provided a means for enhancing there sensitivity to low density of antigen. To block this TCR reorganization we used anti-TCR mAb that sterically separates the TCRs without affecting its antigen recognition site. Furthermore, we showed that TCR reorganization could be affected by changes in the cholesterol content of the cell membrane. Increasing the cholesterol content of the membrane was shown to induce early activation signals.
520 $a In addition to the TCR the role of CD8 in TCR reorganization on the cell surface was investigated. We found that in naive T cells, the presence of CD8 stabilized the interaction of <super>SIY</super>K<super>b</super>-Ig to 2C T cells but not the interaction of <super>QL9</super>L<super>d</super>-Ig with 2C T cells. Second, while the equilibrium binding profiles of <super> QL9</super>L<super>d</super>-Ig was CD8-independent on naive 2C T cells the binding kinetics were very different. Finally, preliminary data showed that the binding of <super>QL9</super>L<super>d</super>-Ig on activated 2C T cells is CD8-dependent showing higher avidities than for activated CD8-T cells. These results highlighted the physiological state of the T cell as a variable in the organization and the function of CD8 as well as the TCR.
590 $a School code: 0098.
650 4 $a Biophysics, General. $3 1019105
650 4 $a Health Sciences, Immunology. $3 1017716
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710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 62-10B.
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