流感病毒交叉反应性记忆T细胞的研究进展

流感病毒是长期威胁人类健康最主要的病毒之一.灭活流感疫苗主要产生针对病毒血凝素的菌株特异性抗体,当新出现的流感病毒株与疫苗株不匹配时,疫苗的有效性将会大大降低.由于季节性流感病毒的抗原漂移和突变的持续出现,人们迫切地需要找到更广泛的保护方式.在以往的研究中,人们逐渐意识到细胞免疫的重要性,尤其是预先存在的记忆T细胞能靶...     

免疫突触的形成及其介导的分子识别

T细胞和APC细胞相互作用形成免疫突触涉及到连续发生的一系列的分子识别事件,最初APC细胞在趋化因子的作用下向T细胞移动,相遇后在抗原非依赖性的弱的黏附力作用下发生最初的黏附,同时伴随着TCR在APC表面俘获特异性抗原;抗原识别之后,由多种机制使T细胞和APC紧密接触并维持一段时间,随后分开,最终引起T细胞的增殖和分化。对免疫突触形成过程中的分子识别机制目前尚无定论,拓扑模式和数学模式的解释,脂筏和细胞骨架蛋白的重排以及接头蛋白的连接为免疫突触形成中分子的识别提供了一定的依据。     

EB病毒免疫逃逸的分子机制

EB病毒(Epstein-Barr vius,EBV)是一种最广泛的对人类感染的γ疱疹病毒,与人类多种疾病尤其是恶性肿瘤有关。其致病的一个重要条件是能够在人体B细胞中长期潜伏,并且在人体免疫力低下时被激活并增殖,这表明EB病毒存在逃逸宿主细胞免疫的机制。从潜伏期EB病毒基因表达的下调、干扰抗原加工和提呈、调节细胞毒性T细胞(Cytotoxic lymphocyte,CTL)免疫应答、干扰细胞因子的作用、干扰CTL的活动及抑制宿主细胞凋亡、抑制辅助性T细胞1(Helper T cell 1,Th1)免疫应答等方面,对EB病毒免疫逃逸的分子机制作一简要综述。     

重组早孕因子与天然早孕因子的免疫交叉反应

目的:探讨细胞表达的重组早孕因子(CHO-EPF)、大肠杆菌表达的重组早孕因子(BL21-EPF)和天然早孕因子(Native Early Pregnancy Factor,nEPF)之间的免疫交叉反应,寻找制备EPF抗体比较理想的免疫原。方法:采用CHO-EPF、nEPF作为免疫原分别免疫BALB/c小鼠,制备CHO-EPF多抗和nEPF多抗;结合本实验室储备的BL21-EPF鼠单克隆抗体,运用SDS-PAGE、Western blotting及ELISA等方法对nEPF、CHO-EPF、BL21-EPF之间的免疫交叉反应进行检测。结果:三种来源的EPF诱导抗体的效价比较无显著性差异。原核表达BL21-EPF与nEPF诱导的抗体中BL21-EPF单抗能识别nEPF中26 ku和52 ku组分,且抗nEPF多抗也能与BL21-EPF中10 ku组分反应;真核表达CHO-EPF与nEPF诱导的抗体中CHO-EPF多抗能识别nEPF中10 ku和26 ku组分,而nEPF抗体不能与CHO-EPF反应;原核表达BL21-EPF与真核表达CHO-EPF诱导的抗体中CHO-EPF多抗能识别BL21-EPF中10 ku片段,而BL21-EPF单抗不能与CHO-EPF反应。结论:真核源性CHO-EPF、原核源性BL21-EPF、人源性nEPF之间存在一定的交叉反应,在抗体制备过程中用rEPF替代nEPF作为免疫原是可行的。     

细胞分裂素: 代谢、信号转导、交叉反应与农艺性状改良

在高等植物中, 细胞分裂素通过对细胞分裂与分化的调节而广泛参与了对植物生长发育的调控。在过去的10余年, 利用模式植物拟南芥的研究, 在阐明细胞分裂素的代谢、转运与信号转导等方面取得了重要的进展。同时, 关于细胞分裂素与其它信号途径之间存在的广泛交叉反应也受到了人们的注意。根据我们现有的知识, 细胞分裂素信号转导是通过磷酸基团在一个双元组分系统之间的系列传递而完成的, 该过程被称之为“磷酸接力传递”(phosphorelay)。细胞分裂素与其它信号途径的互作可能也主要是通过双元组分系统链接的。双元组分系统中目前已知的主要信号元件不仅表现出功能冗余性, 同时在调控特定的植物生长发育过程时也具有特异性。本文在对细胞分裂素的代谢与转运过程简要评述的基础上,对其信号转导以及与其它信号途径间交叉反应的研究进展进行重点讨论, 并展望细胞分裂素研究对重要农业性状改良的意义。     

细胞分裂素:代谢、信号转导、交叉反应与农艺性状改良

在高等植物中,细胞分裂素通过对细胞分裂与分化的调节而广泛参与了对植物生长发育的调控。在过去的10余年,利用模式植物拟南芥的研究,在阐明细胞分裂素的代谢、转运与信号转导等方面取得了重要的进展。同时,关于细胞分裂素与其它信号途径之间存在的广泛交叉反应也受到了人们的注意。根据我们现有的知识,细胞分裂素信号转导是通过磷酸基团在一个双元组分系统之间的系列传递而完成的,该过程被称之为“磷酸接力传递”（phosphorelay）。细胞分裂素与其它信号途径的互作可能也主要是通过双元组分系统链接的。双元组分系统中目前已知的主要信号元件不仅表现出功能冗余性,同时在调控特定的植物生长发育过程时也具有特异性。本文在对细胞分裂素的代谢与转运过程简要评述的基础上,对其信号转导以及与其它信号途径间交叉反应的研究进展进行重点讨论,并展望细胞分裂素研究对重要农业性状改良的意义。     

植物对逆境交叉适应的分子机制

交叉适应(cross-adaptation)是植物应答复合逆境的主要表现形式,它涉及环境刺激、信号转导、基因表达及细胞代谢调节等.为明确交叉适应的分子机制,本文从活性氧、激素、促细胞分裂原激活性蛋白激酶等方面进行了综述,以深入系统地阐明植物对逆境的响应,为作物抗逆栽培提供经济、高效的途径.     

长链非编码RNA的免疫调节机制研究进展

真核生物的基因表达受多个层面调控,包括染色体水平、DNA水平、转录水平和转录后水平的调控等.长链非编码RNA(lnc RNA)是一类转录本超过200 nt的非编码RNA,其对基因表达的调控涉及上述各个层面,如组蛋白修饰、DNA甲基化的调控、转录的促进和抑制、m RNA的剪辑及对转录因子的调控等.其作用方式复杂多样,可与DNA、mRNA和蛋白质等相互作用而发挥调节作用.LncRNA保守性较差,但其表达却有较高的细胞、组织和分化阶段特异性.免疫系统的发育和分化受到精密的调控,且具有较高的阶段性和特异性.因此研究lnc RNA的功能及作用机制,免疫系统是较好的选择,这能促进我们对免疫调控的理解,为免疫性疾病的治疗提供新的思路和方法.本文主要介绍lnc RNA的分类和lnc RNA作用的一般分子机制,及其对T细胞、B细胞、固有免疫细胞和炎症因子的分子调控机制及其进展.     

CD4+T细胞免疫识别的一种新理解

获得性免疫具有抗原特异性,但同时T细胞识别却有混杂性和NHC制约等现象,这提示T细胞对抗原肽-MHC分子复合物(pMHC)识别中可能存在不同模式。本文提出了CD4 T细胞有两种特异性识别活化基础单位(具有不同的生理学意义)的模型,一种为纯TCR模式(TCR model),对pMHC(尤其是抗原肽)高特异性识别;另一种为复合受体模式(TCR-CD4 model),对MHC-Ⅱ分子特异性要求很高(NHC制约),但有可以不同亲合度结合抗原肽的混杂性;它们在免疫应答中以不同组合形式出现,可形成细胞水平区分“自我”与“非我”的效应。由此可更合理、简化地理解各种有关免疫现象以及淋巴免疫系统的起源。     

细胞重编程的分子机制

细胞重编程,尤其是诱导多能性干细胞的出现,给再生医学带来极大的希望。近年来,这方面的研究吸引了众多科学家的参与,也取得了非常丰富的成果。本文主要从转录因子、表观遗传和信号转导等角度,介绍了细胞重编程分子机制研究方面的进展和未来的方向。     

Molecular mechanisms of tumor angiogenesis

The maintenance of growth of malignant tumors is closely related with the development of the vascular network supplying the tumor with blood. The vascularization of tumor tissue is similar to physiological angiogenesis, but in tumors it has some specific features. During the last 25 years a vast number of biomolecules have been found and described which are involved in the regulation of tumor angiogenesis. This review considers the action mechanisms and specific features of expression of the main angiogenic growth factors, such as the vascular endothelium growth factor (VEGF), angiopoietins (Ang-1, Ang-2), and the basic fibroblast growth factor (bFGF). The roles of cytokines, growth factors, proteolytic enzymes, and cell adhesion molecules in the regulation of the key steps of blood vessel generation in the tumor are considered. The significance of angiogenesis in the treatment of oncological diseases and possible approaches for inhibition of the regulatory signals of angiogenic factors are discussed.     

控制植物器官大小的分子机理

植物器官大小是植物形态的一个重要特征并受严格的遗传调控。器官大小与两个不同的过程有关：细胞扩张和细胞分裂。分子遗传分析已经鉴定了许多基因,这些基因通过作用于其中一个或两个过程来影响器官的最终大小。某种植物个体间器官大小的差异是由控制该器官特征的基因表达水平变化引起的,通过拟南芥的遗传分析显示这些基因是如何受控制或被修饰的。以上这些资料阐明了植物如何确定继续或停止生长,同时也提供了改变植物积累生物量的方法。     

The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling

CD148 is a receptor-like protein tyrosine phosphatase up-regulated on T cells after T cell receptor (TCR) stimulation. To examine the physiologic role of CD148 in TCR signaling, we used an inducible CD148-expressing Jurkat T cell clone. Expression of CD148 inhibits NFAT (nuclear factor of activated T cells) activation induced by soluble anti-TCR antibody, but not by antigen-presenting cells (APCs) loaded with staphylococcal enterotoxin superantigen (SAg) or immobilized anti-TCR antibody. Immunofluorescence microscopy revealed that the extracellular domain of CD148 mediates its exclusion from the immunologic synapse, sequestering it from potential substrates. Targeting of the CD148 phosphatase domain to the immunologic synapse potently inhibited NFAT activation by all means of triggering through the TCR. These data lead us to propose a model where CD148 function is regulated in part by exclusion from substrates in the immunologic synapse. Upon T cell-APC disengagement, CD148 can then access and dephosphorylate substrates to down-regulate prolongation of signaling.     

Crystal structure of a cross-reaction complex between an anti-HIV-1 protease antibody and an HIV-2 protease peptide

The monoclonal antibody 1696, elicited by HIV-1 protease, inhibits the activity of both HIV-1 and HIV-2 proteases with inhibition constants in the low nanomolar range. The antibody cross-reacts with peptides derived from the N-terminal region of both proteases. The crystal structure of the recombinant single-chain Fv fragment of 1696 complexed with an N-terminal peptide from the HIV-2 protease has been determined at 1.88A resolution. Interactions of the peptide with scFv1696 are compared with the previously reported structure of scFv1696 in complex with the corresponding peptide from HIV-1 protease. The origin of cross-reactivity of mAb1696 with HIV proteases is discussed.     

Anti-CeHV1 antibodies of two cynomolgus macaques cross-react with HSV2 but not HSV1 antigens in ELISA

BACKGROUND: The aim of the study was to compare the cross-reactivity of macaque anti-CeHV1 antibodies with type 1 and type 2 human herpes simplex viruses (HSV1 and HSV2). METHODS: We studied the serum of 344 animals which had been tested either positive (n = 39) or negative (n = 305) for the presence of CeHV1 antibodies by expert laboratories. Macaque serums were studied by means of two ELISA: one based on HSV1 antigen-coated wells, the other on polystyrene beads coated with HSV1 and HSV2 antigens in approximately equal proportions. RESULTS: In the serum of two animals originating from Vietnam, we found anti-CeHV1 antibodies cross-reacting with HSV2 but not with HSV1 antigens. For the serum with the highest titer, inhibition by soluble antigens confirmed the high affinity of the antibodies for HSV2 antigens. CONCLUSIONS: Tests using HSV1 and HSV2 in a combined way are better suited to macaque screening than tests using only HSV1 antigens.     

Molecular mechanisms of programmed cell death

Programmed cell death is currently under active investigation. A recent meeting focused on the molecular machinery of programmed cell death and on its role in the pathogenesis of human diseases.     

Molecular mechanisms of asymmetric divisions in mammary stem cells

Stem cells have the remarkable ability to undergo proliferative symmetric divisions and self‐renewing asymmetric divisions. Balancing of the two modes of division sustains tissue morphogenesis and homeostasis. Asymmetric divisions of Drosophila neuroblasts (NBs) and sensory organ precursor (SOP) cells served as prototypes to learn what we consider now principles of asymmetric mitoses. They also provide initial evidence supporting the notion that aberrant symmetric divisions of stem cells could correlate with malignancy. However, transferring the molecular knowledge of circuits underlying asymmetry from flies to mammals has proven more challenging than expected. Several experimental approaches have been used to define asymmetry in mammalian systems, based on daughter cell fate, unequal partitioning of determinants and niche contacts, or proliferative potential. In this review, we aim to provide a critical evaluation of the assays used to establish the stem cell mode of division, with a particular focus on the mammary gland system. In this context, we will discuss the genetic alterations that impinge on the modality of stem cell division and their role in breast cancer development.     

Molecular mechanisms of homologous and heterologous desensitization mediated by vasopressin in smooth muscle cells

Arginine vasopressin (AVP) has been shown previously to enhance phosphatidylinositol (PI) turnover and mobilize calcium in the rat aortic smooth muscle cell-line (A10; ATCC CRL 1476) via the V1 receptor (Aiyar, N., Nambi, P., Stassen, F. L., and Crooke, S. T. (1986) Life Sci. 39, 37-45). Exposure of A10 cells to AVP for periods ranging from 5 min to 2 h resulted in 30-40% loss in AVP-binding sites and an inhibition of the production of inositol di- and trisphosphates and the mobilization of calcium when the cells were rechallenged by addition of AVP. We now report that during the same time course AVP induces a dose- and time-dependent decrease in labeled PI, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate reaching a minimum after 30 min of incubation. After 2 h of exposure to AVP, the levels of labeled PI, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate increased to a new basal level approximately 30% less than the untreated cultures. The decrease in inositol lipid labeling mediated by AVP was inhibited when the V1 antagonist SK&F 100273 was included in the incubations with AVP. No decrease was observed when the V2 agonist 1-deamino, [8-D-arginine]vasopressin was used for pretreatment of the cells. Furthermore, when PI kinase activity was measured in cell extracts from untreated and AVP-treated (2 h) cells a significant decrease (p less than 0.05) was observed in the absence, but not in the presence, of added PI in the AVP-treated cells as compared with the control cells. Thrombin also stimulates PI metabolism and calcium mobilization in these cells and brought about both a prolonged decrease in inositol lipids and inhibition of PI kinase activity. AVP pretreatment affected the release of intracellular Ca2+ induced by AVP, thrombin, and ATP, differently. The time of AVP pretreatment required to induce half-maximal inhibition of intracellular Ca2+ release in response to AVP, thrombin, and ATP was approximately 8, 24, and 30 min, respectively. Consequently, we suggest that the reduction in response to AVP with short term preincubation is due to homologous desensitization as reflected by 30-40% decrease in V1 receptors. Subsequently, a decrease in inositol lipid pools and PI kinase activity results in heterologous desensitization in response to AVP, thrombin, and ATP.