Effect of Herpes Simplex Virus-2 Infection in Vitro on the Expression of HLA Class II Antigen of Monocytes

Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.

Diversity and Frequencies of HLA Class I and Class II Genes of an East African Population

Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.

HLA-II类基因与妊娠期糖尿病相关性的研究

有关HLAII类基因的研究已经涉及到遗传学、免疫学、临床医学。其中HLAII与自身免疫性疾病的相关性是非常重要且引人注目的问题,特别是HLAII类基因与糖尿病相关性研究已取得了一定的结论,HLAII类基因与病理性妊娠的相关研究也有所进展。妊娠期糖尿病的病因及发病机理目前尚不清楚。妊娠期糖尿病为糖尿病的一独立特殊型,它与HLAII类基因相关性的研究已开始起步,不同的HLAII类基因可能控制妊娠期糖尿病的抑制性和易感性。

华东地区汉族HLA-Ⅱ类基因与白癜风临床特征的相关性

目的探讨华东地区汉族HLA-Ⅱ类基因与白癜风临床特征的相关性。方法采用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)方法检测华东地区汉族白癜风患者HLA-DRB1、DQA1和DQB1位点的等位基因,使用SPSS10.0统计软件分析。结果HLA-DQA10103与伴发内分泌疾病的患者有显著正相关,DRB109与C4降低的患者明显负相关。按临床类型分析,发现局限型与DRB109和DQA103正相关,非节段型与DQA103正相关。结论:在华东地区汉族人群中,白癜风的临床特征与HLA-Ⅱ类基因有一定的相关性。

HLA-DQ分子遗传结构与中国人重症肌无力的相关性

重症肌无力与HLAⅡ类基因关联性在不同人种和民族中具有不同遗传易感性。为探讨中国人重症肌无力（MG）与HLA－DQ分子关联性，采用聚合酶链式反应－限制性片段长度多态性（PCR－RFLP）方法，分析了50例中国正常人及49例重症肌无力患者的HLA-DQAl和一DQBl座位的基因型。结果：共检出正常人DQAl等位基因8种，DQBl等位基因10种，重症肌无力患者DQAl等位基因8种，DQBl等位基因9种。结果分析表明DQAl*0501与MG呈负相关，DQB1*0302与MG呈正相关。DQA1*0301－DQB1*0302单体型在MG患者中显著增多。从基因水平首次用PCR－RFLP方法得出中国人重症肌无力DQ分子的易感单体型。

HLA-DPB1等位基因与中国人重症肌无力相关性研究

目的：探讨在中国汉族人群中重症肌无力（ＭＧ）与ＨＬＡＩ类基因的关联性。方法：随机抽取了５９例重症肌无力患者的外周血ＤＮＡ，用聚合酶链式反应限制性片段长度多态性（ＰＣＲＲＦＬＰ）方法，分析了其ＨＬＡＤＰＢ１座位的基因型，并与正常对照进行比较。结果：发现ＨＬＡＤＰＢ１０４０２与ＭＧ呈负相关（１１．８６％ｖｓ．２６．９２％；ｒ＝０．１８４３，Ｐｃ＝０．０２８９，ＰＦ＝０．２２０３）；１９０１与ＭＧ则呈正相关（１５．２５％ｖｓ．０．９６％；ｒ＝６．２０８１，Ｐｃ＜０．０１，ＥＦ＝０．０６９０）。结论：ＨＬＡＤＰＢ１座位在ＭＧ的发病过程中具有重要作用。

HLAⅡ类基因区与1型糖尿病

目的 :综述HLAⅡ类基因区与1型糖尿病的关系。方法 :查阅国外有关文献20余篇加以综述。结果 :HLAⅡ类基因区内的DQ、DR基因位点与1型糖尿病具有相关性。结论

肾移植术后抗HLA-Ⅱ类抗体阳性患者与移植肾功能和长期存活的研究

目的研究肾移植术后抗人类白细胞抗原（HLA）-Ⅱ类抗体阳性患者与移植肾功能和长期存活。方法对2007年在首都医科大学附属北京友谊医院已检测出抗HLA-Ⅱ类抗体阳性的肾移植术后107例患者,于2010年和2011年再次检测其抗HLA-Ⅱ类抗体,并在2014年10月前后进行肾功能和长期存活观察。结果 2007年检测出107例肾移植术后抗HLA-Ⅱ类抗体阳性患者,其中19例患者肾功能正常,2010-2011年检测仍阳性,2014年检测肾功能正常。43例患者肾功能正常,2010-2011年检测抗HLA-Ⅱ类抗体转阴性,2014年肾功能正常。2例患者肾功能正常,2010-2011年查抗体转阴性,肾功能正常,2014年肾功能下降。3例患者肾功能正常,2010-2011年查抗体转阴性,肾功能下降,2014年肾功能无再次下降趋势。18例患者肾功能正常,2010-2011年查抗HLA-Ⅱ类抗体阳性,大部分患者肾功能下降,2014年时肾功能全部下降。22例患者肾功能正常,2~3年后移植肾失功或失联。结论抗HLA-Ⅱ类抗体对移植肾功能的影响因人而异,也可能存在保护性抗体。

HLA allele frequencies in Iranian opticospinal multiple sclerosis patients<br>——HLA in Opticospinal MS

Background: In Iranian patients with opticospinal multiple sclerosis (OSMS), a paucity of brain lesions and short spinal cord lesions extending less than three spinal segments are characteristic findings on magnetic resonance imaging (MRI). It also shows a relatively benign course with negative CSF oligo-coonal bands. Objective: We aimed to clarify the possible relationship between clinical phenotype and MRI features of OSMS and human leucocyte antigen (HLA) system in Iran. Methods: Genotyping of HLA class II allele frequencies in 20 patients with OSMS were done, using polymerase chain reaction sequence-specific primer amplification method. Blood samples were extracted and typed for HLA-DRB, DQA, and DQB loci and compared with 100 controls. Results: Significant positive association was observed in DRB1*03, DQA1*0201, DQA1*03, DQB1*0201, and DQB1*0611, while DQB1*0602 was absent in our patients. Conclusion: These finding suggest that HLA-DRB association pattern in OSMS is different from conventional MS in Iran which is mostly associated with DRB1*1501 and from similar Japanese OSMS who are negative for brain lesions fulfilling the Barkhof criteria and negative for the presence of longitudinally extensive spinal cord lesions who carries the DRB*0405 allele. OSMS is immunogenetically heterogeneous. Also absence of DQB1*0602 allele may negatively be associated with the absence of Barkhof brain lesion.

转染CD80(B7-1)基因前后人肿瘤细胞系表面标志表达

动物实验证实协同刺激分子CD80(B7-1)是促进抗肿瘤免疫应答的重要分子.本文应用RT-PCR,FACS技术检测了人肿瘤细胞系及EBV转化的B细胞CD80的表达,结果表明除Raji细胞、EBV转化的B细胞CD80阳性外,3AO、MCF-7、MDA-453、MKN-45、Hela细胞均为阴性.用我室建立的CD80逆转录病毒载体转染包装细胞PA317,筛选高滴度病毒上情感染人肿瘤细胞,得到CD80阳性表达的肿瘤细胞克隆.利用转染前后的人乳腺癌细胞系MDA-453作ICAM-I、HLA class Ⅰ、classⅡ分子表达的分析,结果表明转染有CD80基因的MDA-453细胞ICAM-Ⅰ、HLA classⅠ分子表达上调,class Ⅱ分子的表达未见改变.

结核分枝杆菌RD1区T细胞表位分布情况预测及分析

[目的]对结核分枝杆菌RD1区T细胞表位分布情况进行预测和分析。[方法]利用NetMHC server生物信息学软件,以和HLA-Ⅱ和HLAⅠ-类分子结合能力为指标,分别对结核分枝杆菌RD1区9个编码蛋白进行T细胞抗原表位预测。[结果]通过预测,共获得和HLA-Ⅱ类分子结合的抗原表位1 580个和HLA-Ⅰ类分子结合的抗原表位336个。[结论]预测获得的T细胞抗原表位将对结核病特异性检测及新的结核疫苗研发起到借鉴作用。

Epstein-Barr virus infection mechanisms

Epstein-Barr virus(EBV) infection occurs by distinct mechanisms across different cell types. EBV infection of B cells in vitro minimally requires 5 viral glycoproteins and 2 cellular proteins. By contrast, infection of epithelial cells requires a minimum of 3 viral glycoproteins, which are capable of interacting with one or more of 3 different cellular proteins. The full complement of proteins involved in entry into all cell types capable of being infected in vivo is unknown. This review discusses the events that occur when the virus is delivered into the cytoplasm of a cell, the players known to be involved in these events, and the ways in which these players are thought to function.

The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma

Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated.The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital.We performed whole-exome sequencing(WES)on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC,and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment.Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance.WES and RNA-seq data between lung squamous cell carcinoma(SCC)and adenocarcinoma(Aden)were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS,as analyzed by multivariate Cox proportional hazard regression(P=0.031).The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment.Relatively low expression of HLA class II genes and checkpoint molecules,and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules,as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.

Improving <i>in Silico</i>Prediction of Epitope Vaccine Candidates by Union and Intersection of Single Predictors

The in silico prediction of peptide binding affinities to MHC proteins is a very important first step in the process of epi-tope-based vaccine design and development. Five MHC class II binding prediction servers were combined in different ways and the resulting performance of these combinations was evaluated using a test set, which consisted of 4540 known HLA-DRB1 binders. The five servers were: NetMHCIIpan, NetMHCII, ProPred, RANKPEP, and EpiTOP. The top 5% of the ranked predictions from each server were combined using union and intersection operators. The outputs were evaluated in terms of sensitivity and positive predictive value (PPV). The union operator showed high sensitivity (65-79%) and low PPVs (6-8%), while intersection outputs had low sensitivities (4-41%) yet significantly higher PPVs (14-31%). Thus there is a defining trade-off between sensitivity and PPV for each combination. The union of outputs from different servers brings more “noise” than “signal” to the resulting set of predicted binders. Conversely, selecting only commonly predicted binders increases the probability that an identified binder is a true binder.

上海地区汉族人HLA-DQB1启动子多态性以及QBP-DQB1连锁分析

为分析上海地区汉族人HLA DQB1启动子 (QBP )多态性 ,以及QBP与DQB1的连锁不平衡 ,我们选用 2 4个序列特异性寡核苷酸探针 (SSO )检测QBP多态性。在目前已知的 12种QBP等位基因中 ,我们仅检测到 10种 (未发现新的QBP类型 ) ,并且发现QBP与DQB1的某些等位基因之间存在一定的连锁格局。我们的结果与高加索人群研究结果比较发现 ,无论是QBP基因频率还是QBP DQB1单元型频率 ,在两种不同人群中都存在明显差异。结果提示 ,由于不同的QBP等位基因功能不同 ,因此QBP DQB1之间不同的单倍型组合可能是HLA与疾病关联的另一个因素。

Graves病患者外周血单核细胞膜上HLA-Ⅱ类抗原表达的改变

采用间接免疫荧光技术检测了未经治疗的Graves病患者和健康人外周血单核细胞膜上HLA-DR和HLA-DQ抗原的表达,并分析患者血清T_3、T_4、TSH水平与其单核细胞膜上HLA-DR和HLA-DQ抗原表达间的相关关系。结果表明:病人组HLA-DR^+和HLA-DQ^+单核细胞百分率(分别为57.42±8.73％和20.92±7.28％,±s)均显著低于正常对照组(分别为79.92±5.74％和40.33±6.34％,±s,P<0.001);患者血清TSH水平与其单核细胞膜上HLA-DQ抗原表达间存在显著正相关(r=0.687,P<0.05)。这些结果提示:Graves病患者体内存在单核细胞异常。