T細胞受體活化反應之模型; Modeling T-cell receptor activation

Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/46446

Title:	T細胞受體活化反應之模型;Modeling T-cell receptor activation
Authors:	葉愛慧;Ai-Hui Yeh
Contributors:	生物物理研究所
Keywords:	T細胞受體;T細胞活化;免疫反應;immune response;CD45;TCR activation;T-cell receptor
Date:	2011-01-28
Issue Date:	2011-06-04 15:52:54 (UTC+8)
Publisher:	國立中央大學
Abstract:	本論文提出一個模型來描述T細胞受體的活化反應。T細胞在辨認帶有病毒蛋白質片段的主要組織相容性複合體(agonist pMHC)時，具有高度的專一性、靈敏度，以及能在短時間內迅速反應之特性。在T細胞受體活化反應過程中也需要蛋白質CD45的協助。我們將單一個T細胞受體活化反應過程簡化為一個對於自由的T細胞受體( free TCR) 和TCR-pMHC複合體而言皆為具有可逆修飾作用的反應模型，並且研究kinetic proofreading mechanism及CD45在T細胞受體活化反應中的效用。研究結果顯示，(1)在缺乏CD45時，kinetic proofreading在合理範圍的pMHC濃度下無法幫助T細胞降低出錯率，其主要原因是由於自由的T細胞受體的去活化速率太過緩慢所導致。(2)當有CD45存在時，T細胞受體可加速進行去活化反應。因此當活化反應所經過的步驟較多時，在模擬中self pMHC幾乎很難使T細胞受體達到完全活化的階段。由此可知CD45對於T細胞受體活化反應的專一性而言是不可缺少的。另外，增加活化反應步驟的數目也有助於提高T細胞受體的專一性。(3) 如果在活化反應過程中，未與pMHC形成複合體的T細胞受體不擴散到T細胞與抗原呈現細胞間最近接觸區域之外，則此T細胞受體就有機會能再和pMHC分子產生鍵結並繼續進行其活化反應。藉由這種方式，self pMHC便能夠協助T細胞受體進行活化反應，並有助於提高T細胞受體活化反應之靈敏度與加快活化反應速率。 We propose a model that describes the initial process of T-cell receptor (TCR) activa- tion. An e cient T cell can recognize agonist pMHC with high speci city, sensitivity, and speed. The assistance of CD45 is also required for TCR activation. We consider the simulation for single TCR activation that is simpli ed as a reversible modi cation levels for both free TCR and TCR-pMHC complex. We discuss the e cacy of kinetic proofreading mechanism and CD45 in TCR activation. Our study reveals that (i) In the absence of CD45, kinetic proofreading fails at reasonable pMHC concentrations due to the slowness of deactivation processes for free TCR. (ii) In the presence of CD45, TCR can be deactivated quickly. Even when there are few activation steps, it is di cult that self pMHC fully activate the TCR during the simulation. It means that CD45 is very essential for the speci city of TCR activation and increasing the number of activation steps is helpful for TCR speci city. (iii) If a free TCR does not di use out of the close contact region between the T cell and the antigen-presenting cell, it can bind with a pMHC and continues to move to higher activation level. That indicates the possibility for self pMHC to help TCR activation, and it may eventually explain the sensitivity and speedy of TCR activation.
Appears in Collections:	[Graduate Institute of Biophysics] Electronic Thesis & Dissertation

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