抗原的加工和提呈

抗原的加工有两条不同的途径：一条是内源性抗原途径,抗原在内质网（ＥＲ）和高尔基器内加工并与ＭＨＣＩ类分子结合后被提呈到细胞表面,加工后的抗原能被具有ＣＤ８分子的Ｔ细胞识别：另一条是外源性抗原途径,抗原在内吞体（ｅｎｄｏｓｏｍｅ）被加工降解并与ＭＨＣⅡ类分子结合后转运到细胞表面,它可被具有ＣＤ４分子的Ｔ辅助细胞（ＴＨ）识别。本从分子生物学角度描述了两条加工途径的合同制,为某些疾病的诊断和免疫治疗,     

Ⅱ类抗原提呈的分子机制及分子伴侣Ii研究进展

本文综述MHC Ⅱ抗原提呈的分子机制,并着重对MHC Ⅱ抗原提呈通路中的分子伴侣恒定链(Invariant chain,Ii)的结构、功能研究的近期进展作了回顾,对近年来开展起来的利用Ii链作为内源性靶向载体,将目的抗原表位内源性靶向MHC Ⅱ抗原结合凹槽的研究进行了简单的综述,内源性靶向为疫苗设计提供了很好的思路,可以应用于病原微生物、肿瘤和变态反应性疾病的治疗和预防中。     

PLGA人工抗原提呈细胞载体的制备

目的:目前常用的载体材料,在体内很难降解,限制了其在体内的应用,本文通过用PLGA微球制备人工抗原提呈细胞(AAPC)载体,对其功能进行验证.希望此方法能弥补传统方法的不足.方法:将软脂酸偶联到亲和素上,然后按照传统的复乳法来制备PLGA微球,并且通过使用荧光素(FITC)标记、生物素化的牛血清蛋白(BSA)对其功能进行验证.结果:通过该方法可以得到表面固定生物素的PLGA微球,并且证明软脂酸修饰并未影响到亲和素分子和生物素的结合,生物素化的BSA分子可以有效的结合到微球的表面.结论:PLGA微球表面很难引进合适的化学基团,导致其不能像聚苯乙烯微球那样通过化学反应来将亲和素分子固定在微球的表面上,通过将软脂酸偶联到亲和素分子上,可改变其表面很难引进合适的化学基团的不足,用其微球可用于制备AAPC载体.人工抗原提呈细胞是免疫学研究领域的新思路,可在基础免疫研究和临床治疗方面发挥较大的作用,但作为一门新兴技术,在制备、效果评价及应用方面需要逐渐完善和成熟,用PLGA微球为载体构建,弥补了磁珠、聚苯乙烯不能在体内降解的不足,且安全无毒,可供参考.     

DNA传感器及其免疫信号传导通路的研究新进展

DNA于哺乳动物细胞质中的存在是一个危险信号,提示机体内微生物感染的存在。近五年来的研究显示,细胞质DNA的传导机制是免疫系统产生免疫应答的分子基础。迄今为止已报道多种DNA传感器,其中STING是一个关键的衔接蛋白,参与大部分DNA信号传导途径。最近,c GAS-c GAMP第二信使通路、IFI16及其他传感器的发现为解析胞质DNA识别的分子机制提供了新见解。这些重要的发现有助于了解宿主防御系统,提高疫苗免疫原性,为感染性疾病的预防与治疗提供新思路。     

鱼类DNA疫苗研究的新进展

疫苗及其预防接种是控制动物病原疾病、保障养殖业持续发展的重要手段。     

组织蛋白酶S在抗原提呈过程中的作用

效应T细胞激活需要两个或以上的信号诱导.抗原肽结合MHC-Ⅱ分子的溶酶体途径（第一信号）包括两个重要的步骤：不变链（invariant chain Ii）降解和抗原加工.目前所知的溶酶体蛋白酶中,组织蛋白酶S（cathepsin S,cat S）被认为以非冗长的作用参与了上述两步过程,其还参与了降解细胞外基质（extracellular matrix,ECM）的过程.因此被认为在调节免疫、自身免疫性疾病、抗肿瘤免疫、组织重塑等方面是具有潜力的研究靶点.     

人喉癌组织中浸润树突状细胞抗原提呈效应的形态学研究

目的:探讨人喉癌组织中肿瘤浸润树突状细胞(tumor infiltrating dendritic cell,TIDC)肿瘤抗原提呈效应。方法:采用光镜、透射电镜和免疫组化方法观察28例手术切除的人喉癌中TIDC和肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)的形态学表现。结果:早期人喉癌组织中TIDC主要分布在癌周区及癌巢内,病变早期TIDC和TIL的浸润比晚期明显(P<0．01)。透射电镜下可见形态不一的TIDC和TIL广泛分布于癌巢边缘、游走于癌周边组织的血管和淋巴管周围。TIDC与肿瘤细胞、TIDC与TIL、TIL与TIL、TIL与肿瘤细胞之间存在多种形式的膜接触。与TIL接触的肿瘤细胞,细胞核均质化。细胞膜消失呈凋亡状态。癌晚期TIDC与TIL数量明显减少,于癌巢内常见凋亡的TIDC与TIL。结论:人喉癌组织中存在不同形态的TIDC与TIL,TIDC、TIL、癌细胞彼此密切接触发生免疫应答反应,TIDC、TIL的数量和活跃状态与肿瘤进展密切相关。     

DNA疫苗在肌内编码抗原并与免疫原性相关

该研究证明了DNA疫苗注射后在肌肉组织中产生了病毒抗原,并用黄病毒系统检验了其在小鼠中与抗体产生的关系。为达到抗原生产的检测性水平,作者使用了无针注射器,并用夹心酶联免疫吸附法检查了10％的四头肌匀浆物中的病毒抗原,比较了抗登革1型(名为pcD1ME)、     

禽流感病毒感染食蟹猴肺组织内抗原提呈细胞亚型分析

目的分析禽流感病毒感染的食蟹猴肺组织内抗原提呈细胞的不同亚型。方法收集中国医学科学院实验动物研究所病理室禽流感病毒H5N1亚型感染的食蟹猴肺组织蜡块标本,观察其病理学变化及运用免疫组织化学的方法进一步分析CD68、CD14及S-100在感染禽流感病毒食蟹猴肺组织中的表达。结果禽流感病毒感染的肺组织内肺间隔增宽伴巨噬细胞为主的炎细胞浸润,肺泡腔内可见血浆蛋白及纤维素渗出。部分肺泡间隔断裂、巨噬细胞及淋巴细胞浸润。肺组织内H5N1病毒抗原染色呈阳性。肺间隔及肺泡内可见大量CD68阳性细胞,局部可见散在CD14和S-100阳性细胞。结论禽流感病毒感染的食蟹猴肺组织内抗原提呈细胞主要以巨噬细胞为主。     

树突状细胞和癌症的免疫学治疗

树突状细胞(dendritc cells,DC)是一种抗原提呈细胞,能特异地引发和调控机体免疫。它具有抗原呈现功能而不损害免疫系统,不仅能够激活CD4^ 辅助T细胞和CD8^ 细胞毒性T细胞,还能活化B细胞和自然杀伤细胞。已有的研究让人们看到了癌症疫苗的希望,但还处于早期阶段,有许多尚未确定的因素。因此有关DC疫苗用于对肿瘤的保护性和治疗性免疫还有待于进一步的研究。     

活载体疫苗的研究进展

免疫学与生物工程等领域取得的巨大进步,为发展基因工程疫苗提供了更多的理论和技术支持。活载体疫苗(Live Vector Vaccine,LVV),是以细菌或病毒作为外源抗原和治疗因子的载体系统,是目前最具发展潜力的基因工程疫苗之一。不同疫苗载体、抗原呈递方式和对宿主细胞免疫系统启动机制等研究的深入,开拓了活载体疫苗的实用价值。对国际上相关研究予以重点综述,以期为深入开展该领域研究提供依据。     

Antibody response in mice immunized with a plasmid DNA encoding the colonization factor antigen I of enterotoxigenic Escherichia coli

The colonization factor antigen I (CFA/I) is one of the most epidemiologically relevant enterotoxigenic Escherichia coli (ETEC) fimbrial adhesins, which mediates the binding to human small intestine epithelium. A recombinant eukaryotic expression plasmid, pRECFA, encoding the CFA/I protein fused to the glycoprotein D of herpes simplex type 1 virus, was used to generate an antibody response in a murine model following intramuscular inoculation of purified DNA. Eukaryotic cells (BHK-21) transfected with pRECFA expressed the CFA/I protein in vitro, as revealed by Western blot and immunofluorescence microscopy. Administration of a single pRECFA 100-microg dose induced a long-term CFA/I-specific antibody response in BALB/c mice composed mainly of IgG and, to a lesser extent, IgA isotypes. The major CFA/I-specific IgG subclass was IgG2a, suggesting a Th-1-type immune response. A second dose with the same amount of purified DNA, given 2 weeks later, caused a booster effect on the immunoglobulin levels, but did not qualitatively alter the isotypes and subclasses of the induced antibody response. Immunization with different amounts of purified DNA and/or number of doses showed that maximal transient CFA/I-specific antibody levels could be obtained after two 100-microg doses of pRECFA given 2 weeks apart, but long-term antibody levels were similar.     

Antigen presentation between T cells drives Th17 polarization under conditions of limiting antigen

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Comparison of PSA-specific CD8<Superscript>+</Superscript> CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins

The ability of heat shock proteins (HSPs) to increase the potency of protein- and DNA-based vaccines has been previously reported. We have constructed several plasmid-based vectors encoding chimeric proteins containing prostate-specific antigen (PSA) fused to Mycobacterium tuberculosis hsp70, M. bovis hsp65, Escherichia coli DnaK (hsp70), or human hsp70. Immunizing mice with these plasmids induced CD8⁺ cytotoxic T lymphocytes (CTLs) specific to human PSA and protected mice from a subsequent subcutaneous challenge with PSA-expressing tumors. We did not observe a significant difference either in the levels of PSA-specific CTLs or in protection against tumor challenge in mice immunized with plasmids expressing PSA-HSP chimeric proteins, as compared to mice receiving a conventional PSA-expressing DNA plasmid. Our data indicate that using HSPs as fusion partners for tumor-specific antigens does not always result in the enhancement of antigen-specific CTL responses when applied in the form of DNA vaccines.     

Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans

Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.     

Proteasome and class I antigen processing and presentation

The recent discovery of two proteasome homologous genes,LMP2 andLMP7, in the class II region of the human MHC, has implicated this multi-subunit protease in an early step of the immune response; the degradation of intracellular and viral proteins. Short peptides produced by the proteasome are transported into the ER by the product of another set of MHC class II genes,TAP1 andTAP2, where they bind and stabilise HLA class I molecules. Antigenic peptides displayed at the cell surface by HLA class I molecules mark cells for destruction by cytotoxic T lymphocytes. The role of the proteasome in antigen processing was questioned when mutant cells, which lack theLMP genes, were able to process and present antigens normally. The discovery that two proteasome -subunits, delta andMB1, highly homologous toLMP2 andLMP7 and expressed in reciprocal manner, is now consistent with a role for the proteasome in antigen processing. The incorporation of different -subunits into the proteasome may be a mechanism to modulate catalytic activity of the proteasome complex, allowing production of peptides that are more suitable to enter into the ER by the TAP transporters and to bind HLA class I molecules. But, in the absence of the LMPs, the other subunits permit processing of most antigens reasonably efficiently.Abbreviations ABC ATP-binding cassete - 2m 2-microglobulin - ER endoplasmic reticulum - IFN interferon - LMP low molecular weight peptide - MHC major histocompatibility complex - TAP transporter associated with antigen processing     

Employing proteomics in the study of antigen presentation: an update

Introduction: Our immune system discriminates self from non-self by examining the peptide cargo of human leukocyte antigen (HLA) molecules displayed on the cell surface. Successful recognition of HLA-bound non-self peptides can induce T cell responses leading to, for example, the destruction of infected cells. Today, largely due to advances in technology, we have an unprecedented capability to identify the nature of these presented peptides and unravel the true complexity of antigen presentation.

Areas covered: In addition to conventional linear peptides, HLA molecules also present post-translationally modified sequences comprising a wealth of chemical and structural modifications, including a novel class of noncontiguous spliced peptides. This review focuses on these emerging themes in antigen presentation and how mass spectrometry in particular has contributed to a new view of the antigenic landscape that is presented to the immune system.

Expert Commentary: Advances in the sensitivity of mass spectrometers and use of hybrid fragmentation technologies will provide more information-rich spectra of HLA bound peptides leading to more definitive identification of T cell epitopes. Coupled with improvements in sample preparation and new informatics workflows, studies will access novel classes of peptide antigen and allow interrogation of rare and clinically relevant samples.