• IMMUNE NETWORK
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• 제23권2호
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• pp.17.1-17.16
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• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2001년도 가을 학술발표논문집 Vol.28 No.2 (1)
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• pp.415-417
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• 2001

HLA(High Level Architecture)는 차세대 DIS(Distributed Interactive Simulation)를 이어 네트워크 분산 시뮬레이션의 기반이 되는 표준 아키텍쳐이다. 이 HLA 시스템의 개발 과정에서 FEDEP(Federation Development and Execution Process) Model이 제안되었는데, FEDEP의 목적은 federation 개발자가 application의 요구를 충족시킬 수 있도록 federation 개발 및 실행에 대한 guideline을 정하는 것이다. FEDEP의 일련의 process들 중에서 노동집약적인 과정은 CASE(Computer Aided Software Engineering) tool을 사용함으로써 보다 강화되고 능률적으로 이루어질 수 있다. 본 논문에서 소개하는 HLA Application Builder 는 federate 와 federation을 자동적으로 생성하는 CASE tool 로서, 자동적인 FED(Federation Execution Data)file 및 C++ source code를 생성함으로써 HLA Federation 개발에 있어서의 인력(manpower)을 크게 줄일 수 있다. 본 논문에서는 HLA에 대한 배경지식과 HLA Application Builder 개발의 필요성과 구현, 그리고 실제 예를 들어서 HLA Application Builder가 어떻게 federation 개발에 사용되는지에 대해서 설명한다.

• 한국시뮬레이션학회:학술대회논문집
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• 한국시뮬레이션학회 2002년도 추계학술대회 논문집
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• pp.85-89
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• 2002

Development of distributed simulation environment must be required in order to simulate the distributed models regionally and inter-operate with running simulations individually, Simulation based on DEVS formalism is difficult to simulate the distributed models. DEVS formalism is modeling methodology. To specify model, this formalism separates behavior and structure, therefore it is able to design complex model easily. HLA is standard framework of distribute simulation environment, It is defined to facilitate the interoperability and the reusability. RTI (Run Time Infrastructure) is software that provides common service to simulation systems and implementation of the HLA Interface Specification. Method of implementation is that modules cooperating with RTI are added to simulator on DEVS simulation environment. On the DEVS simulation environment (DEVS-Obj -C) that already developed, Highest class of abstract simulator uses service that RTI provide, then This environment is able to change DEVS model into Federate and run distribute simulation that inter-operates with the RTI. Because this distributed simulation environment includes convenience of modeling that obtains through the DEVS formalism and accompanies HLA standard, this environment make it possible to simulate with_ complex systems and heterogeneous simulations

• 대한임상검사과학회지
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• 제40권2호
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• pp.94-97
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• 2008

The human leukocyte antigen (HLA) is the name of the major histocompatibility complex (MCH) in humans. The superlocus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6. and encode cell surface antigen-presenting proteins and many other genes. HLA class I antigen (A, B & C) present peptides from inside the cell. These peptides are produced from digested proteins that are broken down in the lysozymes. Most expressed HLA loci exhibit a remarkable degree of allelic polymorphism, which derives from sequence differences predominantly localized to discrete hypervariable regions of the amino terminal domain of the molecule. In this sutdy, the HLA-A genotypes were determined in twenty students unrelated koreans using the PCR-SSP (Polymerase Chain Reaction-Sequence Specific Primer) technique. Several specific primer pairs in assigning the HLA-A gene were used (A*0201, A*33, A*2401). The results of PCR-SSP, the HLA-A*0201 primer was detected eleven (55%), the HLA-A*33 were detected seven (35%) and the HLA-A*2401 were detected seven (35%). This study shows that the PCR-SSP technique is relatively simple, fast and a practical tool for the determination of the HLA-A genotypes.

• BMB Reports
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• 제38권3호
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• pp.350-353
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• 2005

Alanine at residue 73 (Ala-73) and aspartate at residue 9 (Asp-9) are characteristic to both Cw6 and Cw7 alleles of HLA-C gene and have been suggested as possible markers for psoriasis vulgaris (PsV). However, the results from various ethnic groups/populations are contradictory and inconclusive. In this study, an attempt has been made to examine the association between HLA-C (Ala-73 and Asp-9) and susceptibility to PsV among Saudi patients. Genomic DNA was extracted from 25 Saudi PsV patients and 75 control subjects. Polymerase chain reaction (PCR) was performed to amplify HLA-C sequences using earlier reported primers, C133P and C243PR. Sequence-specific primers were used to specifically detect nucleotide coding for Ala-73 and Asp-9 in all the subjects. The results showed significantly higher frequency of Asp-9 (84.0% versus 61.3%) in PsV patients as compared to controls (p < 0.05, 2-tailed Fisher's exact test). The frequencies of Ala-73 among PsV patients (92%) and controls (88%) did not differ significantly.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4427-4433
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• 2013

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to be associated with cervical cancer risk, but results have varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that $B^*51$:01:02 allele frequency was significantly higher in patients with SCC than in healthy controls ($P=3.17{\times}10^{-5}$, $P_c$=0.005, OR=26.7). Statistical analysis also revealed a significantly decreased frequency of $B^*51$:01:02 ($P=7.01{\times}10^{-4}$, $P_c$=0.03, OR=0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-$B^*51$:01:02 may confer susceptibility to SCC and HLA-$B^*51$:01:02 may contribute to resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, indicating the individual allele associations to be independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC.

• 대한수혈학회지
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• 제24권3호
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• pp.233-240
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• 2013

배경: 수혈의 기왕력이 항HLA항체의 형성과 연관이 있다는 사실은 잘 알려져 있다. 하지만, 특발성 혈소판 감소성 자반증의 주 표적은 혈소판의 당단백이며, 당단백 항체와 항 HLA class I 항체의 형성기전은 완전히 다른 것이다. 이번 연구의 목적은 특발성 혈소판 감소성 자반증 환아의 항HLA class I 항체의 임상적 의미를 찾아 보고자 함에 있다. 방법: 1990년부터 2010년까지 경상대학교병원을 방문한 48명의 대조군과 48명의 특발성 혈소판감소성자반증 환아들을 대상으로 하였다. 각각의 환자들의 혈청을 Modified Antigen Capture Enzyme-linked immunosorbent assay (MACE) kit를 이용하여 항 당단백 항체와 항 HLA class I 항체를 검사하였다. 결과: 두 그룹간의 항 HLA class I항체의 양성률은 의미 있는 차이를 보였으며[36/39 (92.3%) vs 29/46 (63.0%)][혈소판감소성자반증 환자군 vs 정상대조군] (P=0.002), 항HLA class I 평균항체 S/C ratio 또한 의미 있는 차이를 보였다(3.55 vs 1.51) [혈소판감소성자반증 환자군 vs 정상대조군] (P=0.0000). 하지만 혈소판 감소성 자반증 환자군에서 수혈을 받은 환자들과 수혈을 받지 않은 환자들 간의 항HLA항체 양성률은 의미 있는 차이를 보이지 않았으며[12/12 (100%) vs 24/27 (88%)][수혈을 받은 환자군 vs 비수혈 환자군](P=0.22), 평균 항체 S/C ratio 또한 통계적으로 의미 있는 차이를 보이지 않았다(4.30 vs 3.25)[수혈을 받은 환자군 vs 비수혈 환자군](P=0.22). 수혈 이후에 추적검사를 위해 채혈을 했던 환아들의 샘플을 이용한 항체 양성률 및 항체가 검사에서도 의미 있는 차이는 없는 것으로 나타났다. 결론: 항 HLA class I 항체는 혈소판 감소성 자반증과 연관이 있을 수 있으나, 수혈은 혈소판 감소성 자반증 환아의 임상적 경과에 영향을 미치지 못한다.

• IMMUNE NETWORK
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• 제2권4호
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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.

• 한국국방경영분석학회지
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• 제30권1호
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• pp.81-91
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• 2004

Since HLA (High Level Architecture) was selected as a standardized distributed simulation architecture by US DoD in order to guarantee interoperability among all types of simulations, weapons system and C4I systems, to improve reusability of developed models in mid 1990s, a large number of federates have been developed and certified in accordance with HLA specifications. This paper illustrates case studies on HLA compliance test which are helpful for developers and managers. Based on experiences obtained from international HLA compliance test of CJ21_NG being developed for ground warfare simulation during ROKA's BCTP and UFL exercises, compliance procedures of US Defense and Modelling Simulation Office (DMSO) are introduced, and detail information at each phase of compliance test is provided.

• Genomics & Informatics
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• 제17권3호
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• pp.29.1-29.8
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• 2019

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.