• Title, Summary, Keyword: HLA-E

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The effect of progesterone and 17-β estradiol on membrane-bound HLA-G in adipose derived stem cells

  • Moslehi, Akram;Hashemi-beni, Batool;Moslehi, Azam;Akbari, Maryam Ali;Adib, Minoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.341-346
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    • 2016
  • Membrane-bound HLA-G (mHLA-G) discovery on adipose derived stem cells (ADSCs) as a tolerogenic and immunosuppressive molecule was very important. Many documents have shown that HLA-G expression can be controlled via some hormones such as progesterone (P4) and estradiol (E2). Therefore, this study was designed to evaluate progesterone and estradiol effects on mHLA-G in ADSCs at restricted and combination concentrations. Three independent cell lines were cultured in complete free phenol red DMEM and subcultured to achieve sufficient cells. These cells were treated with P4, E2 and P4 plus E2 at physiologic and pregnancy concentrations for 3 days in cell culture conditions. The HLA-G positive ADSCs was measured via monoclonal anti HLA-G-FITC/ MEMG-09 by means of flow cytometry in nine groups. Data were analyzed by one way ANOVA and Tukey's post hoc tests. There were no significant values of the mean percentage of HLA-G positive cells in E2-treated and the combination of P4 plus $E_2-treated$ ADSCs compared to control cells (p value>0.05) but P4 had a significant increase on mHLA-G in ADSCs (p value<0.05). High P4 concentration increased mHLA-G but E2 and the combination of P4 plus E2 could not change mHLA-G on ADSCs.

Identification of a Novel Fusion Gene (HLA-E and HLA-B) by RNA-seq Analysis in Esophageal Squamous Cell Carcinoma

  • Jiang, Yu-Zhang;Li, Qian-Hui;Zhao, Jian-Qiang;Lv, Jun-Ji
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2309-2312
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    • 2014
  • Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.

Implementation of the submarine diving simulation in a distributed environment

  • Ha, Sol;Cha, Ju-Hwan;Roh, Myung-Il;Lee, Kyu-Yeul
    • International Journal of Naval Architecture and Ocean Engineering
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    • v.4 no.3
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    • pp.211-227
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    • 2012
  • To implement a combined discrete event and discrete time simulation such as submarine diving simulation in a distributed environment, e.g., in the High Level Architecture (HLA)/Run-Time Infrastructure (RTI), a HLA interface, which can easily connect combined models with the HLA/RTI, was developed in this study. To verify the function and performance of the HLA interface, it was applied to the submarine dive scenario in a distributed environment, and the distributed simulation shows the same results as the stand-alone simulation. Finally, by adding a visualization model to the simulation and by editing this model, we can confirm that the HLA interface can provide user-friendly functions such as adding new model and editing a model.

Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy

  • Kim, Sunghoon;Chung, Hye Won;Kong, Hoon Young;Lim, Jong-Baeck
    • Yonsei Medical Journal
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    • v.58 no.1
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    • pp.43-50
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    • 2017
  • Purpose: To identify new immunogenic $HLA-A^*33;03-restricted$ epitopes from the human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical cancer. Materials and Methods: We synthesized fourteen overlapping 15-amino acid peptides and measured intracellular $interferon-{\gamma}$ ($IFN-{\gamma}$) production in PBMC and CD8+ cytotoxic T lymphocytes (CTLs) after sensitization with these peptides using flow cytometry and ELISpot assay. The immunogenicity of epitopes was verified using a $^{51}Cr$ release assay with SNU1299 cells. Results: Among the fourteen 15-amino acid peptides, $E7_{49-63}$ (RAHYNIVTFCCKCDS) demonstrated the highest $IFN-{\gamma}$ production from peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with $E7_{49-63}$ showed higher cytotoxic effect against SNU1299 cells than did CD8+ CTLs sensitized with other peptides or a negative control group. Thirteen 9- or 10-amino acid overlapping peptides spanning $E7_{49-63}$, $E7_{50-59}$ (AHYNIVTFCC), and $E7_{52-61}$ (YNIVTFCCKC) induced significantly higher $IFN-{\gamma}$ production and cytotoxic effects against SNU1299 cells than the other peptides and negative controls, and the cytotoxicity of $E7_{50-59}$- and $E7_{52-61}$-sensitized PBMCs was induced via the cytolytic effect of CD8+ CTLs. Conclusion: We identified $E7_{50-59}$ and $E7_{52-61}$ as novel HPV 16 E7 epitopes for $HLA-A^*33;03$. CD8+ CTL sensitized with these peptides result in an antitumor effect against cervical cancer cells. These epitopes could be useful for immune monitoring and immunotherapy for cervical cancer and HPV 16-related diseases including anal cancer and oropharyngeal cancer.

Family Study of TAP Gene Polymorphism and HLA-TAP Haplotypes in Koreans (가계조사를 통한 한국인의 TAP 유전자의 다형성과 HLA-TAP 일배체형 분포에 관한 연구)

  • Whang, Dong Hee;Park, Myoung Hee
    • IMMUNE NETWORK
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    • v.2 no.4
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    • pp.248-255
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    • 2002
  • Background: TAP1 and TAP2 are two ABC transporter genes located within the class II region of the human MHC. Their protein products form a heterodimer whose function is to transport peptides from the cytoplasm into the endoplasmic reticulum. This study was performed to examine the polymorphism of TAP genes and the distribution of HLA-TAP haplotypes in the Korean population through family analysis. Methods: The subjects used in this study were 50 healthy Korean families consisting of 233 individuals. TAP1 (codons 333 and 637) and TAP2 (codons 379, 565, 577, 651, 665, and 687) typings were carried out by the PCR-restriction fragment length polymorphism (RFLP) method. HLA-DRB1 and DQB1 genotyping results from a previous study were used for HLA-TAP haplotype analysis. Results: The number (gene frequency) of TAP1 and TAP2 alleles detected were 3 for TAP1 (A 81.5%, B 17.0%, and C 1.5%) and 8 for TAP2 (A1 32.0%, A2 12.5%, B 34.0%, Bky2 6.5%, C 7.0%, D 3.0%, E 4.5%, and G 0.5%). Eleven TAP1-TAP2 haplotypes were observed with $frequency{\geq}1%$, among which 4 haplotypes (A-B, B-A1, A-Bky2, and C-E) showed weak but significant positive linkage disequilibrium (P<0.05). When DRB1-DQB1 haplotypes were extended to TAP1 and TAP2 loci, much diversification of haplotypes was observed: 19 different DRB1-DQB1 haplotypes formed 58 different haplotypes extended to TAP1 and TAP2 loci. These results add more evidence to the view that recombination hotspot is present within and around TAP gene region. Conclusion: The allele frequencies of TAP1 and TAP2 genes and the distribution of TAP1-TAP2 and HLA-TAP haplotypes were studied in Koreans based on a family study.

Association Between HLA-DQ Genotypes and Haplotypes vs Helicobacter pylori Infection in an Indonesian Population

  • Zhao, Yang;Wang, Jingwen;Tanaka, Tsutomu;Hosono, Akihiro;Ando, Ryosuke;Soeripto, Soeripto;Triningsih, F.X. Ediati;Triono, Tegu;Sumoharjo, Suwignyo;Astuti, E.Y. Wenny;Gunawan, Stephanus;Tokudome, Shinkan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1247-1251
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    • 2012
  • Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

Immunologic Aspects at the Feto-Maternal Interface (태아모체간 계면에서의 면역학적 측면)

  • 정인배
    • Development and Reproduction
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    • v.5 no.2
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    • pp.93-100
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    • 2001
  • Precise mechanism by which the fetus can escape from mother's immune rejection is not well understood yet over the last 50 years. The clarification of immune mechanism at the feto-maternal interface is very important, because this can be a common pathogenesis of various pathologic conditions including spontaneous abortion, habitual abortion fetal growth restriction preeclampsia, implantation failure after assisted reproductive techniques, and fetal death. In this review, current hypothetical contents were described with the priority of importance: 1) The center of this mechanism is cross-talk between the expression of HLA-C, E, G on the extravillous cytotrophoblasts and their receptors on decidual NK cell, 2) immunomodulation, 3) innate immunity is the main immunologic mechanism, 4) various mechanisms besides HLA system(eq. complement) may be associated. The overall balance of immunomodulation among these mechanisms should result in the outcome of each pregnancy. Further researches regarding the regulation of HLA system, roles of cytokines, complements should be followed in the future.

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Prediction of Promiscuous Epitopes in the E6 Protein of Three High Risk Human Papilloma Viruses: A Computational Approach

  • Nirmala, Subramanian;Sudandiradoss, Chinnappan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4167-4175
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    • 2013
  • A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, Epi,Jen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.

Generation of Anti-HLA-DR4 Specific Antibodies by Immunization of the Recombinantly Expressed Allelic Subtype-Specific Region of the $HLA-DRB1^*0405$ Molecules

  • Park, Jung-Hyun;Cho, Eun-Wie;Lee, Yun-Jung;Chung, Jin;Hahm, Kyung-Soo;Kim, Kil-Lyong
    • BMB Reports
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    • v.31 no.2
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    • pp.111-116
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    • 1998
  • HLA-DR4 is the dominant allele of MHC class II genes in Koreans. In particular, the $DRB1^*0405$ subtype has been reported to be almost exclusively expressed in Far East Asians, and has also been observed to be strongly associated with rheumatoid arthritis in Koreans and the Japanese. Identification of this specific allele has been mainly performed by PCR-based methods, which is often time consuming, costly, and involves tedious procedures such as the isolation of genomic DNA, PCR, and gel electrophoresis. To develop a more convenient tool for screening vast amounts of samples as well as to generate reagents which might also be used in other applications, in this study, antibodies were produced against this specific HLA subtype. By PCR, an allelespecific region covering the ${\beta}1$ domain of $DRB1^*0405$ was amplified and recombinantly expressed in E.coli. Immunization of Lewis rats with the purified protein yielded an allele specific antiserum. Western blot analysis showed the selective detection of the HLA-DR ${\beta}-chain$. Using this antiserum, established cell lines and peripheral blood lymphocytes were analyzed on their HLA haplotype by fluorescence activated flow cytometry. These novel antibodies will provide a powerful tool in the detection and investigation of DR4 alleles.

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Genetics of Alzheimer's Disease

  • Kim, Jong Hun
    • Dementia and Neurocognitive Disorders
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    • v.17 no.4
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    • pp.131-136
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    • 2018
  • Alzheimer's disease (AD) related genes have been elucidated by advanced genetic techniques. Familial autosomal dominant AD genes founded by linkage analyses are APP, PSEN1, PSEN2, ABCA7, and SORL1. Genome-wide association studies have found risk genes such as ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-HLA-DRB1, INPP5D, MEF2C, MS4A6A/MS4A4E, NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1. ABCA7, SORL1, TREM2, and APOE are proved to have high odds ratio (>2) in risk of AD using next generation sequencing studies. Thanks to the promising genetic techniques such as CRISPR-CAS9 and single-cell RNA sequencing opened a new era in genetics. CRISPR-CAS9 can directly link genetic knowledge to future treatment. Single-cell RNA sequencing are providing useful information on cell biology and pathogenesis of diverse diseases.