EGFP標(biāo)記的小鼠K~b分子在RAW246.7中的表達(dá)及其交叉遞呈功能的初步研究
本文選題:交叉遞呈 + 綠色熒光蛋白; 參考:《第三軍醫(yī)大學(xué)》2005年碩士論文
【摘要】: T淋巴細(xì)胞識別由主要組織相容性復(fù)合物(MHC)I或II類分子遞呈的抗原肽片段。對于MHC-I類分子而言,經(jīng)典的抗原遞呈理論認(rèn)為胞漿內(nèi)合成的蛋白質(zhì)抗原在胞漿中蛋白酶體的作用下被裂解為小的肽段,隨后在抗原加工相關(guān)轉(zhuǎn)運體(TAP)的作用進入內(nèi)質(zhì)網(wǎng)(ER),與其中的MHC-I類分子相結(jié)合,并形成穩(wěn)定的MHC-I-肽復(fù)合物,然后從ER轉(zhuǎn)運到高爾基體和細(xì)胞膜表面,供CD8+T細(xì)胞識別。而外源性抗原經(jīng)胞吞或胞飲作用進入抗原遞呈細(xì)胞(APC)的內(nèi)體系統(tǒng),被其中的酸敏蛋白酶降解,然后與位于晚期內(nèi)體和溶酶體樣結(jié)構(gòu)中的MHC-II類分子相結(jié)合,并由其遞呈給CD4+T細(xì)胞。 然而,26年前在器官移植中發(fā)現(xiàn),宿主的抗原遞呈細(xì)胞可以激發(fā)宿主對供者細(xì)胞次要組織相容性抗原的免疫應(yīng)答,這一現(xiàn)象現(xiàn)被稱為交叉遞呈。大量研究表明,多種抗原均可經(jīng)此途徑引起CD8+T細(xì)胞的免疫應(yīng)答。交叉遞呈在清除不能感染APC的病毒、自身MHC-I類分子下調(diào)的腫瘤組織以及維持外周耐受方面都發(fā)揮著重要作用,因此,闡明交叉遞呈的細(xì)胞和分子機制是十分必要的?蔀榕R床疾病的治療及疫苗設(shè)計提供新思路。 對于交叉遞呈的胞內(nèi)途徑一直以來有兩種認(rèn)識。其中之一認(rèn)為外源性抗原進入內(nèi)吞囊泡后依靠特殊的轉(zhuǎn)運機制或者內(nèi)吞囊泡膜的破裂而釋放其中的抗原到胞漿中,然后沿著經(jīng)典的MHC-I類途徑被遞呈給CD8+T細(xì)胞。另一種觀點認(rèn)為交叉遞呈發(fā)生于內(nèi)體系統(tǒng)中,抗原被其中酸敏的蛋白酶體水解,和由細(xì)胞膜上循環(huán)而至的MHC-I類分子相結(jié)合,隨后被轉(zhuǎn)運到細(xì)胞表面。最近,有文獻報道在外源性抗原的交叉遞呈過程中,ER可以和吞噬體相互融合,后者從ER中獲得MHC-I類遞呈途徑所需要的各種分子。這一模型的提出為交叉遞呈的研究提供了新思路。 關(guān)于交叉遞呈中MHC-I類分子及其和抗原肽形成復(fù)合物后的轉(zhuǎn)運途徑還不明確,上述模型也多是從生化角度加以論證。有研究表明部分病毒以及腫瘤組織之所以不能被機體免疫系統(tǒng)有效識別,就是因為其干擾了胞內(nèi)MHC-I類分子至胞膜的轉(zhuǎn)運,而并非以前認(rèn)為的抑制MHC-I類分子的合成。因此,明確MHC-I類分子在交叉遞呈過程
[Abstract]:T lymphocytes recognize antigenic peptide fragments presented by major histocompatibility complexes (MHCI or II). For MHC-I molecules, the classical antigen-presenting theory suggests that the protein antigens synthesized in the cytoplasm are split into small peptides under the action of the proteasome in the cytoplasm. Then TAP, a transporter associated with antigen processing, enters the endoplasmic reticulum (ER), binds to the MHC-I molecules, and forms a stable MHC-I- peptide complex, which is then transported from ER to Golgi apparatus and cell membrane for recognition by CD8 T cells. The exogenous antigens enter the inner system of antigen-presenting cells through cytosolic or cytosolic action, and are degraded by acid-sensitive proteases, and then combined with MHC-II molecules located in the late inosomes and lysosomal structures. And it was presented to CD4 T cells. However, in organ transplantation 26 years ago, it was found that host antigen-presenting cells can stimulate the host's immune response to donor cell secondary histocompatibility antigen, which is now known as cross-presentation. A large number of studies have shown that many kinds of antigens can induce immune response of CD8 T cells in this way. Cross-presentation plays an important role in the clearance of viruses that cannot be infected with APC, the down-regulation of tumor tissues by their own MHC-I molecules and the maintenance of peripheral tolerance. Therefore, it is necessary to elucidate the cellular and molecular mechanisms of cross-presentation. It can provide a new idea for the treatment of clinical diseases and vaccine design. There have been two understandings of the intracellular pathway of cross-presentation. One of them suggested that exogenous antigens were released into the cytoplasm by special transport mechanism or rupture of endocytic vesicle membrane, and then presented to CD8 T cells along the classical MHC-I pathway. In another view, cross-presentation occurs in the inner body system, in which the antigen is hydrolyzed by the acid-sensitive proteasome, combined with the MHC-I molecules circulating on the cell membrane, and then transported to the cell surface. Recently, it has been reported that ER can fuse with phagocysts during cross-presentation of exogenous antigens, and the latter can obtain various molecules needed for the MHC-I presenting pathway from ER. This model provides a new idea for the research of cross-presentation. The transport pathways of MHC-I molecules and their complexes with antigenic peptides in cross-presentation are not clear, and the above models are also demonstrated from the biochemical point of view. Some studies have shown that some viruses and tumor tissues can not be effectively recognized by the body's immune system because it interferes with the transport of MHC-I class molecules to the cellular membrane, rather than inhibiting the synthesis of MHC-I class molecules as previously thought. Therefore, it is clear that MHC-I molecules in the cross-presentation process
【學(xué)位授予單位】:第三軍醫(yī)大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2005
【分類號】:R392
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