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author:("Choi, daewon")
1.  Communication, Opponents, and Clan Performance in Online Games: A Social Network Approach 
Online gamers form clans voluntarily to play together and to discuss their real and virtual lives. Although these clans have diverse goals, they seek to increase their rank in the game community by winning more battles. Communications among clan members and battles with other clans may influence the performance of a clan. In this study, we compared the effects of communication structure inside a clan, and battle networks among clans, with the performance of the clans. We collected battle histories, posts, and comments on clan pages from a Korean online game, and measured social network indices for communication and battle networks. Communication structures in terms of density and group degree centralization index had no significant association with clan performance. However, the centrality of clans in the battle network was positively related to the performance of the clan. If a clan had many battle opponents, the performance of the clan improved.
PMCID: PMC3870575  PMID: 23745617
2.  Identification of HLA-A*0201-Restricted Cytotoxic T Lymphocyte Epitopes Derived from HLA-DOβ as a Novel Target for Multiple Myeloma 
British journal of haematology  2013;163(3):343-351.
Despite the recent development of effective therapeutic agents against multiple myeloma (MM), new therapeutic approaches, including immunotherapies, remain to be developed. Here we identified novel human leucocyte antigen (HLA)-A*0201 (HLAA2)-restricted cytotoxic T lymphocyte (CTL) epitopes from a B cell specific molecule HLA-DOβ (DOB) as a potential target for MM. By DNA microarray analysis, the HLADOB expression in MM cells was significantly higher than that in normal plasma cells. Twenty-five peptides were predicted to bind to HLA-A2 from the amino acid sequence of HLA-DOB. When screened for the immunogenicity in HLA-A2-transgenic mice immunized with HLA-DOB cDNA, 4 peptides were substantially immunogenic. By mass spectrometry analysis of peptides eluted from HLA-A2-immunoprecipitates of MM cell lines, only two epitopes, HLA-DOB232-240 (FLLGLIFLL) and HLA-DOB185-193 (VMLEMTPEL), were confirmed for their physical presence on cell surface. When healthy donor blood was repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific γ-interferon secretion, HLA-DOB232-240 was more immunogenic than HLA-DOB185-193. Additionally, the HLA-DOB232-240-specific CTLs, but not the HLA-DOB185-193-specific CTLs, displayed an major histocompatibility complex class I-restricted reactivity against MM cell lines expressing both HLA-A2 and HLA-DOB. Taken together, based on the physical presence on tumour cell surface and high immunogenicity, HLA-DOB232-240 might be useful for developing a novel immunotherapy against MM.
PMCID: PMC4137325  PMID: 24032635
multiple myeloma; HLA-DOβ; cytotoxic T lymphocyte; T cell epitope; DNA microarray
4.  Impaired Tumor Antigen Processing by Immunoproteasome-expressing CD40-Activated B cells and Dendritic Cells 
Professional APCs, such as dendritic cells, are routinely used in vitro for the generation of cytotoxic T lymphocytes specific for tumor antigens. In addition to dendritic cells, CD40-activated B cells and variant K562 leukemic cells can be readily transfected with nucleic acids for in vitro and in vivo antigen presentation. However, the expression of immunoproteasome components in dendritic cells may preclude display of tumor antigens such as Mart1/MelanA. Here, we use three target epitopes, two derived from tumor antigens [Mart126–34 (M26) and Cyp1B1239–247 (Cyp239)] and one derived from the Influenza A viral antigen [FluM158–66 (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens. In contrast, the K562 HLA-A*0201 transfectant efficiently processes and presents M26 and Cyp239 as well as the influenza FluM58 epitopes to T cells. These results demonstrate that the choice of target APC for gene transfer of tumor antigens may be limited by the relative efficacy of proteasome components to process certain tumor epitopes. Importantly, K562 can be exploited as an artificial APC, efficient in processing both M26 and Cyp239 epitopes and presumably, by extension, other relevant tumor antigens.
PMCID: PMC3547125  PMID: 21400024
Vaccination; Tumor Immunity; Antigen Processing; Dendritic Cells
5.  Graft-versus-leukemia antigen CML66 elicits coordinated B and T cell immunity after donor lymphocyte infusion 
The target antigens of graft-versus-leukemia that are tumor-associated are incompletely characterized.
Experimental Design
We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI).
From this patient, CML66-reactive CD8+ T cell clones were detected against an endogenously presented HLA-B*4403-restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T cell responses were detectable in peripheral blood before DLI. However, by one month after DLI, CD8+ T cells were present in peripheral blood, and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow prior to DLI by ELISpot and by a nested polymerase chain reaction-based assay to detect clonotypic T cell receptor sequences, but not in blood of the patient pre-DLI, nor of the graft donor.
CD4+ DLI results in rapid expansion of pre-existing marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus demonstrates that durable post-transplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens, that elicit coordinated cellular and humoral immunity.
PMCID: PMC2872105  PMID: 20460482
Donor lymphocyte infusion; graft-versus-leukemia; leukemia antigen; chronic myeloid leukemia; T cell
6.  Overexpression of X-linked Inhibitor of Apoptosis Protein (XIAP) is an Independent Unfavorable Prognostic Factor in Childhood de Novo Acute Myeloid Leukemia 
Journal of Korean Medical Science  2009;24(4):605-613.
The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression. This study was performed to investigate the prognostic relevance of XIAP expression in childhood acute myeloid leukemia (AML). In 53 children with de novo AML, the level of XIAP expression was determined by using quantitative reverse transcriptase-polymerase chain reaction and was analyzed with respect to the clinical characteristics at diagnosis and treatment outcomes. As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014). In addition, XIAP overexpression (≥median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a worse 3-yr relapsefree survival rate (52.7±20.9% vs. 85.9±14.8%, P=0.014). Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013). Collectively, XIAP overexpression may be used as an unfavorable prognostic marker in childhood AML.
PMCID: PMC2719207  PMID: 19654940
X-Linked Inhibitor of Apoptosis Protein; Apoptosis; Inhibitor of Apoptosis Protein; Leukemia, Myeloid, Acute
7.  Neuronal Apoptosis Inhibitory Protein is Overexpressed in Patients with Unfavorable Prognostic Factors in Breast Cancer 
Journal of Korean Medical Science  2007;22(Suppl):S17-S23.
Neuronal apoptosis inhibitory protein (NAIP) is a recently identified inhibitor of apoptosis protein. However, the clinical relevance of NAIP expression is not completely understood. In an attempt to determine the clinical relevance of NAIP expression in breast cancer, the levels of NAIP and survivin expression were measured in 117 breast cancer samples and 10 normal breast tissues using quantitative reverse-transcriptase-polymerase chain reaction. While there was no evidence of NAIP expression in the normal breast tissue, NAIP was expressed in all breast cancer samples. The level of NAIP expression in breast cancer was significantly higher (257 times) than in the universal tumor control. There was a strong correlation between the level of NAIP expression and the level of survivin expression (p=0.001). The level of NAIP expression in patients with a large tumor (≥T2) and patients with an unfavorable histology (nuclear grade III) was significantly higher than in those patients with a small tumor (T1) and patients with a favorable histology (nuclear grade I, II) (p=0.026 and p=0.050, respectively). Although the level of NAIP expression was higher in patients with other unfavorable prognostic factors, it was not significant. The three-year relapse-free survival rate was not significantly the patients showing high NAIP expression and patients showing low NAIP expression (86.47±4.79% vs. 78.74±6.57%). Further studies should include the expressions of NAIP in a larger number of patients and for a longer period of follow-up to evaluate correlation with metastasis and treatment outcome. In conclusion, NAIP is overexpressed in breast cancer patients with unfavorable clinical features such as stage and tumor size, suggesting that NAIP would play a role in the disease manifestation.
PMCID: PMC2694398  PMID: 17923748
Breast Cancer; Neuronal Apoptosis Inhibitory rotein (NAIP); Apoptosis; Prognostic Factor; Clinical Relevance
8.  Cotransplanted Bone Marrow Derived Mesenchymal Stem Cells (MSC) Enhanced Engraftment of Hematopoietic Stem Cells in a MSC-dose Dependent Manner in NOD/SCID Mice 
Journal of Korean Medical Science  2006;21(6):1000-1004.
Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by culture in addition to whole bone marrow, has been shown to enhance engraftment of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be an optimum ratio range that could enhance engraftment. We examined the percent donor chimerism according to the ratio of HSCs to MSCs in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of ratios of co-transplanted CD34+-selected bone marrow cells, and marrow-derived MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1×105 bone marrow derived human CD34+ cells were administered to each mouse and human MSCs from different donors were infused concomitantly. We repeated the procedure three times and evaluated engraftment with flow cytometry four weeks after each transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8 and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an excessive dose of MSCs might decrease engraftment efficiency.
PMCID: PMC2721918  PMID: 17179676
Hematopoietic Stem Cells; Mesenchymal Stem Cells; Transplantation; Mice, SCID; Engraftment

Results 1-8 (8)