JC virus-specific CD8+ cytotoxic T lymphocytes are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy. However, very few JC virus T cell epitopes restricted to MHC class I have been defined. Of the two HLA-A*0201-restricted JCV epitopes, VP1p36 and VP1p100, studies have shown that they are conserved T cell epitopes of polyomaviruses. The cross-recognition associated to these epitopes has complicated the efforts of understanding the dynamics of immune response to JC virus. Based on the previously identified HLA-A*0201 binding T cell epitope of Simian virus 40 T antigen P281–289 (KCDDVLLLL) and BK virus T antigen P558–566 (SLQNSEFLL), T cell epitopes of JC Virus T antigen P282–290 (KCEDVFLLM) and P557–565 (SLSCSEYLL) were identified. In this report, we demonstrated that JC Virus P282–290 and P557–565 were able to stimulate T cell responses in healthy donors’ PBMCs and CD8+ cytotoxic T lymphocytes raised with both peptides could recognize and lyse their targets. Most importantly, there were no T cell cross-recognitions between JC Virus, BK Virus and SV40 virus. Therefore, JCV T-ag epitopes P282–290 and P557–565 could be better antigen epitopes compared to VP1p36 and VP1p100 to study the dynamics of cellular immune response to JCV in PML patients. In addition, as a HLA-A*0201 binding T cell epitope, both peptides could be a valuable component of immunotherapies aiming at increasing the cellular immune response against JCV for the treatment of progressive multifocal leukoencephalopathy.
{"title":"Characterization of Non-Conserved HLA-A*0201 Binding T cell Epitopes of JC Virus T Antigen","authors":"Jongming Li, J. Wagner, B. Mookerjee","doi":"10.4137/VRT.S957","DOIUrl":"https://doi.org/10.4137/VRT.S957","url":null,"abstract":"JC virus-specific CD8+ cytotoxic T lymphocytes are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy. However, very few JC virus T cell epitopes restricted to MHC class I have been defined. Of the two HLA-A*0201-restricted JCV epitopes, VP1p36 and VP1p100, studies have shown that they are conserved T cell epitopes of polyomaviruses. The cross-recognition associated to these epitopes has complicated the efforts of understanding the dynamics of immune response to JC virus. Based on the previously identified HLA-A*0201 binding T cell epitope of Simian virus 40 T antigen P281–289 (KCDDVLLLL) and BK virus T antigen P558–566 (SLQNSEFLL), T cell epitopes of JC Virus T antigen P282–290 (KCEDVFLLM) and P557–565 (SLSCSEYLL) were identified. In this report, we demonstrated that JC Virus P282–290 and P557–565 were able to stimulate T cell responses in healthy donors’ PBMCs and CD8+ cytotoxic T lymphocytes raised with both peptides could recognize and lyse their targets. Most importantly, there were no T cell cross-recognitions between JC Virus, BK Virus and SV40 virus. Therefore, JCV T-ag epitopes P282–290 and P557–565 could be better antigen epitopes compared to VP1p36 and VP1p100 to study the dynamics of cellular immune response to JCV in PML patients. In addition, as a HLA-A*0201 binding T cell epitope, both peptides could be a valuable component of immunotherapies aiming at increasing the cellular immune response against JCV for the treatment of progressive multifocal leukoencephalopathy.","PeriodicalId":39174,"journal":{"name":"Virology: Research and Treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/VRT.S957","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70717595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nephropathy associated with BK virus has emerged as an important cause of allograft failure in renal transplant recipients. Here we exploited a recently developed novel monocyte based solid phase T cell selection system, in which monocytes are immobilized on solid support, for antigen-specific T cell purification. The underlying hypothesis of this new method is that antigen-specific T cells recognize, bind their cognate antigens faster than non-specific T cells and are concentrated on the surface after removing the non-adherent cells by washing. Moreover, activated antigen-specific T cells proliferate more rapidly than non-specific T cells, further increasing the frequency and purity of antigen-specific T cells. Optimal selection times for BK virus-specific T cells are studied. Our data demonstrated that T cell selection can usually increase the frequency of antigen-specific T cells by > 10 fold, whereas T cell expansion following the selection boost the frequency of antigen-specific T cells by another ~10 fold. This new T cell selection system is superior to traditional stimulation method (i.e. simply mixing antigen presenting cells and lymphocytes together) in generating antigen-specific T cells. This inexpensive and simple T cell selection system can produce large quantity of highly purified BK virus-specific T cells within 1–2 weeks after initial T cell activation.
{"title":"Generation of BKV-Specific T Cells for Adoptive Therapy against BKV Nephropathy","authors":"Jongming Li, B. Mookerjee, Priya Singh, J. Wagner","doi":"10.4137/VRT.S942","DOIUrl":"https://doi.org/10.4137/VRT.S942","url":null,"abstract":"Nephropathy associated with BK virus has emerged as an important cause of allograft failure in renal transplant recipients. Here we exploited a recently developed novel monocyte based solid phase T cell selection system, in which monocytes are immobilized on solid support, for antigen-specific T cell purification. The underlying hypothesis of this new method is that antigen-specific T cells recognize, bind their cognate antigens faster than non-specific T cells and are concentrated on the surface after removing the non-adherent cells by washing. Moreover, activated antigen-specific T cells proliferate more rapidly than non-specific T cells, further increasing the frequency and purity of antigen-specific T cells. Optimal selection times for BK virus-specific T cells are studied. Our data demonstrated that T cell selection can usually increase the frequency of antigen-specific T cells by > 10 fold, whereas T cell expansion following the selection boost the frequency of antigen-specific T cells by another ~10 fold. This new T cell selection system is superior to traditional stimulation method (i.e. simply mixing antigen presenting cells and lymphocytes together) in generating antigen-specific T cells. This inexpensive and simple T cell selection system can produce large quantity of highly purified BK virus-specific T cells within 1–2 weeks after initial T cell activation.","PeriodicalId":39174,"journal":{"name":"Virology: Research and Treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/VRT.S942","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70717543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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