• Korean Journal of Microbiology
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• v.47 no.4
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• pp.342-347
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• 2011

T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

• Clinical and Experimental Pediatrics
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• v.54 no.7
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• pp.313-315
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• 2011

Reactive arthritis comprises a subgroup within infection-associated arthritides in genetically susceptible hosts. Researchers and clinicians recognize two clinical forms of reactive arthritis which occurs after genitourinary tract infection and after gastrointestinal tract infection. Chlamydia infection has been implicated as the most common agent associated with post-venereal reactive arthritis. Studies have proposed Shigella infection, Salmonella infection, or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 antigen is the best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella enteritis at Pusan National University hospital.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.1
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• pp.20-25
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• 2009

Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of rejection in xenotransplantation is an acute cellular rejection by host $CD8^+$ cytotoxic T lymphocyte (CTL) cells that react to donor major histocompatibility complex (MHC) class I. The human cytomegalovirus (HCMV) glycoprotein Unique Short (US) 2 specifically targets MHC class I heavy chains to relocate them from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study we transfected the US2 gene into minipig fetal fibroblasts and established four US2 clonal cell lines. The integration of US2 into transgenic fetal cells was confirmed using PCR and Southern blot assay. The reduction of Swine Leukocyte Antigen (SLA)-I by US2 was also detected using Flow cytometry assay (FACS). The FACS analysis of the US2 clonal cell lines demonstrated a substantial reduction in SLA-I surface expression. The level (44% to 76%) of SLA-I expression in US2 clonal cell lines was decreased relative to the control. In cytotoxicity assay the rate of $CD8^+$ T cell-mediated cytotoxicity was significantly reduced to 23.8${\pm}$15.1% compared to the control (59.8${\pm}$8.4%, p<0.05). In conclusion, US2 can directly protect against $CD8^+$-mediated cell lysis. These results indicate that the expression of US2 in pig cells may provide a new approach to overcome the CTL-mediated immune rejection in xenotransplantation.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2005.10a
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• pp.131-131
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• 2005

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2005.10a
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• pp.131-131
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• 2005

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.611-614
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• 2009

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of a wide range of autoantibodies, resulting in tissue damage. Although the susceptibility to SLE has been attributed to complex interactions between genetic and environmental factors, the influence of a genetic predisposition to SLE is supported by observations of familial aggregations. Family studies have found that siblings with an SLE-affected relative have a 20-fold higher risk of developing SLE compared with the general population. Here, we present a rare case of two male siblings with SLE. The clinical, laboratory, and histopathological findings of these individuals showed the characteristic features of SLE. Human leukocyte antigen (HLA) typing revealed that the brothers and their mother shared the common HLA haplotype of DRB1*1501 and DQB1*0602, which is significantly associated with disease susceptibility in both family-based and casecontrol studies. This report provides an opportunity to reveal the role of genetic factors in the development of SLE.

• Sleep Medicine and Psychophysiology
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• v.8 no.2
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• pp.107-112
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• 2001

Introduction: Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, is known to be closely associated with the human leukocyte antigen (HLA) DQB1*0602. Several studies have suggested that HLA-DQB1*0602 is strongly linked with narcolepsy-cataplexy. However, no studies have yet been made on whether HLA DQB1*0602 is associated with Korean patients with narcolepsy. This study was designed to investigate the frequency of HLA-DQB1*0602 of Korean patients with narcolepsy. Methods: Twenty patients were selected (mean age: $28.2{\pm}3.0$, 11 men and 9 women). The patients were confirmed to have narcolepsy by the overnight polysomnography and multiple sleep latency test (MSLT) in addition to their clinical history and symptoms at St. Vincent's Hospital and Korea University Hospital Sleep Disorders Clinic. Any subjects co-morbid with other hypersomnic sleep disorders such as sleep apnea or periodic limb movements during sleep were excluded. Clinical data was collected through a semi-structured interview for narcoleptic patients. All patients and 21 control did HLA typing for the presence of DQB1*0602. Results Obtained were as Follows: 1) Mean sleep latency was 2.4 (${\pm}2.0$ minutes) and mean frequency of sleep-onset REM period was 3.0 (${\pm}1.6$) by MSLT. 2) Characteristic symptoms of narcolepsy investigated were as follows: excessive daytime sleepiness (100%), cataplexy (100%), sleep paralysis (60%), hypnagogic hallucination (70%) and disrupted nocturnal sleep (75%). 3) Strong emotional expression such as laughing (80%) and joking (70%) triggered cataplexy which affects the knee and leg region (80%) and jaw region (30%). 4) HLA-DR2 was found in 90% of patients and 35% in controls. The frequency of HLA-DQB1*0602 in patients and controls was 90%, and 24%, respectively. Conclusions: These results, which exhibit high HLA-DQB1*0602 expression in Korean patients with narcolepsy, suggest that HLADQB1*0602 could be a strong genetic marker in narcolepsy.

• Korean Journal of Clinical Laboratory Science
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• v.40 no.2
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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.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.179-184
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• 2006

Background: Identification of antigen-specific T cells has yielded valuable information on pathologic process and the disease state. Assays for quantification of inflammatory cytokines or lytic-granule molecules have been generally used to evaluate antigen specific T cell response, however their applicability have been hampered due to the limited source of autologous antigen-presenting target cells (APC). Methods: K562, a leukemic cell line deficient of human leukocyte antigen (HLA), was transfected with a gene encoding HLA-A*02 (K562/ A*02) and its function as stimulator cells in inducing activation of HLA-matched T cells was evaluated by IFN-${\gamma}$ enzyme linked immunospot (ELISPOT) assay. Results: The stable transfectant K562/ A*02 pulsed with HLA- A*02 restricted peptide could specifically induce IFN-${\gamma}$ secretion by CD8+ T cells compared to no detectable secretion by CD4+ T cells. However, CD56+ NK cells secreted IFN-${\gamma}$ in both K562/ A*02 with peptide and without peptide. The number of IFN-${\gamma}$ secreted CD8+ T cells was increased according to the ratio of T cells to K562 and peptide concentration. Formalin-fixed K562/ A*02 showed similar antigen presenting function to live K562/ A*02. Moreover, K562/ A*02 could present antigenicpeptide to not only A*0201 restricted CD8+ T cells but also CD8+ T cells from A*0206 donor. Conclusion: These results suggest that K562/ A*02 could be generally used as target having specificity and negligible background for measuring CD8+ T cell responses and selective use of K562 with responsder matched HLA molecules on its surface as APC may circumvent the limitation of providing HLA-matched autologous target cells.

• Development and Reproduction
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• v.23 no.2
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• pp.79-92
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• 2019

Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.