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 theexpres...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.展开更多
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 resolutio...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.展开更多
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 r...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.展开更多
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...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.展开更多
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 o...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.展开更多
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 treatm...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.展开更多
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 ...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.展开更多
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金This work was supported by the National Key Technologies R&D Program(Grant No.2015BAI12B12)the National Key R&D Program(Grant No.2018YFC1313400)+2 种基金grants from the National Natural Science Foundation of China(Grant Nos.81802873 and 81672697)the Natural Science Foundation of Tianjin(Grant No.18JCQNJC81300)the Tianjin Municipal Education Commission Program(Grant No.2017KJ197).
文摘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.
文摘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.