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Els Goulmy - One of the best experts on this subject based on the ideXlab platform.
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Minor Histocompatibility Antigen H-Y Is Expressed on Human Hematopoietic Progenitor Cells
2016Co-Authors: Els Goulmy, Willem Fibbe, See Profile, Paul J. Voogt, Willemien F. J. Veenhof, J Frederik H FalkenburgAbstract:Minor Histocompatibility antigen H-Y is expressed on human hematopoietic progenitor cell
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IMMUNOBIOLOGY General
2016Co-Authors: Joke Den M. M. Haan, Tuna Mutis, Els Blokl, Ad P. Ijzerman, Els GoulmyAbstract:T-cell receptor antagonists to immunomodulate HLA-A2–restricted minor Histocompatibility antigen HA-1–specific T-cell response
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GENE THERAPY
2016Co-Authors: Mirjam H M Heemskerk, Els Goulmy, Michel G D Kester, Manja Hoogeboom, Roelof A. De Paus, Roel Willemze, J Frederik H FalkenburgAbstract:Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor Histocompatibility antigen HA-2–specific T-cell receptor complexes expressing a conserved alpha joining regio
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human cytotoxic t lymphocytes specific for a single minor Histocompatibility antigen ha 1 are effective against human lymphoblastic leukaemia in nod scid mice
Leukemia, 2006Co-Authors: L Hambach, J Frederik H Falkenburg, B A Nijmeijer, Z Aghai, M Van Schie, Marca H M Wauben, Els GoulmyAbstract:Human cytotoxic T lymphocytes specific for a single minor Histocompatibility antigen HA-1 are effective against human lymphoblastic leukaemia in NOD/scid mice
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hla class i minor Histocompatibility antigen tetramers select cytotoxic t cells with high avidity to the natural ligand
Hematology Journal, 2000Co-Authors: Geraldine M. Gillespie, Els Goulmy, J Frederik H Falkenburg, Tuna Mutis, Ellen Schrama, Janine Kamp, Bennie Esendam, Paul MossAbstract:Introduction: Cytotoxic T cells specific for the hematopoietic system-restricted minor Histocompatibility antigens HA-1 and HA-2 are potential tools for the treatment of relapsed leukemia after minor Histocompatibility antigen mismatched bone marrow transplantation. HA-1/HA-2-specific cytotoxic T cells with strong cytotoxic activity against HA-1/HA-2 positive target cells can be generated in vitro using HA-1 and HA-2 peptide-pulsed dendritic cells as antigen presenting cells. Material and methods: We used HLA-A2 HA-1/HA-2 tetramers (HA-1 A2 /HA-2 A2 tetramers) to monitor the in vitro generation of HA-1- or HA-2-specific cytotoxic T cells. Results: We show that the intensity of the tetramer-staining of the HA-1/HA-2-specific cytotoxic T cells strongly correlates with their capability to recognize mHag positive target cells. The bright tetramer-staining cytotoxic T cells lyse target cells expressing the natural ligand. The dim tetramer-staining cytotoxic T cells fail to lyse natural ligand positive target cells and lyse peptide-pulsed target cells only. The frequency of bright tetramer-staining, high avidity minor Histocompatibility antigen-specifc CTLs increases significantly upon appropriate antigen-specific restimulations. Conclusion: Our results demonstrate that HLA class I-minor Histocompatibility antigen tetramers are useful tools for monitoring and selection of high avidity HA-1- and HA-2specific cytotoxic T cells for adoptive immunotherapy. The Hematology Journal (2000) 1, 403‐410
J Frederik H Falkenburg - One of the best experts on this subject based on the ideXlab platform.
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Minor Histocompatibility Antigen H-Y Is Expressed on Human Hematopoietic Progenitor Cells
2016Co-Authors: Els Goulmy, Willem Fibbe, See Profile, Paul J. Voogt, Willemien F. J. Veenhof, J Frederik H FalkenburgAbstract:Minor Histocompatibility antigen H-Y is expressed on human hematopoietic progenitor cell
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GENE THERAPY
2016Co-Authors: Mirjam H M Heemskerk, Els Goulmy, Michel G D Kester, Manja Hoogeboom, Roelof A. De Paus, Roel Willemze, J Frederik H FalkenburgAbstract:Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor Histocompatibility antigen HA-2–specific T-cell receptor complexes expressing a conserved alpha joining regio
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human cytotoxic t lymphocytes specific for a single minor Histocompatibility antigen ha 1 are effective against human lymphoblastic leukaemia in nod scid mice
Leukemia, 2006Co-Authors: L Hambach, J Frederik H Falkenburg, B A Nijmeijer, Z Aghai, M Van Schie, Marca H M Wauben, Els GoulmyAbstract:Human cytotoxic T lymphocytes specific for a single minor Histocompatibility antigen HA-1 are effective against human lymphoblastic leukaemia in NOD/scid mice
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hla class i minor Histocompatibility antigen tetramers select cytotoxic t cells with high avidity to the natural ligand
Hematology Journal, 2000Co-Authors: Geraldine M. Gillespie, Els Goulmy, J Frederik H Falkenburg, Tuna Mutis, Ellen Schrama, Janine Kamp, Bennie Esendam, Paul MossAbstract:Introduction: Cytotoxic T cells specific for the hematopoietic system-restricted minor Histocompatibility antigens HA-1 and HA-2 are potential tools for the treatment of relapsed leukemia after minor Histocompatibility antigen mismatched bone marrow transplantation. HA-1/HA-2-specific cytotoxic T cells with strong cytotoxic activity against HA-1/HA-2 positive target cells can be generated in vitro using HA-1 and HA-2 peptide-pulsed dendritic cells as antigen presenting cells. Material and methods: We used HLA-A2 HA-1/HA-2 tetramers (HA-1 A2 /HA-2 A2 tetramers) to monitor the in vitro generation of HA-1- or HA-2-specific cytotoxic T cells. Results: We show that the intensity of the tetramer-staining of the HA-1/HA-2-specific cytotoxic T cells strongly correlates with their capability to recognize mHag positive target cells. The bright tetramer-staining cytotoxic T cells lyse target cells expressing the natural ligand. The dim tetramer-staining cytotoxic T cells fail to lyse natural ligand positive target cells and lyse peptide-pulsed target cells only. The frequency of bright tetramer-staining, high avidity minor Histocompatibility antigen-specifc CTLs increases significantly upon appropriate antigen-specific restimulations. Conclusion: Our results demonstrate that HLA class I-minor Histocompatibility antigen tetramers are useful tools for monitoring and selection of high avidity HA-1- and HA-2specific cytotoxic T cells for adoptive immunotherapy. The Hematology Journal (2000) 1, 403‐410
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mismatches of minor Histocompatibility antigens between hla identical donors and recipients and the development of graft versus host disease after bone marrow transplantation
The New England Journal of Medicine, 1996Co-Authors: Els Goulmy, Alois Gratwohl, R F Schipper, Jos Pool, E Blokland, J Frederik H Falkenburg, J M Vossen, Georgia Boyce Vogelsang, Hans C Van Houwelingen, Jon J Van RoodAbstract:Background Graft-versus-host disease (GVHD) can be a major complication of allogeneic bone marrow transplantation even when the donor and recipient are siblings and share identical major Histocompatibility antigens. The explanation may be a mismatch of minor Histocompatibility antigens. We previously characterized five minor Histocompatibility antigens, HA-1, 2, 3, 4, and 5, that are recognized by T cells in association with the major Histocompatibility antigens HLA-A1 and A2. Methods We collected peripheral-blood leukocytes from 148 bone marrow recipients and their sibling donors, who were genotypically HLA identical. Fifty pairs were positive for HLA-A1, 117 were positive for HLA-A2, and 19 were positive for both. The pairs were typed with cytotoxic-T-cell clones specific for minor Histocompatibility antigens HA-1, 2, 3, 4, and 5. Results Mismatches of HA-3 were equally distributed among recipients in whom GVHD developed and those in whom it did not. By contrast, a mismatch of only HA-1 was significantl...
Derry C Roopenian - One of the best experts on this subject based on the ideXlab platform.
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the immunogenomics of minor Histocompatibility antigens
Immunological Reviews, 2002Co-Authors: Derry C Roopenian, Evan Young Choi, Aaron C BrownAbstract:Minor Histocompatibility (H) antigens are a diverse assemblage of major Histocompatibility complex (MHC)-bound peptides with the unifying property of acting as alloantigens that induce allogeneic tissue rejection. They are a consequence of any form of accumulated genetic variation that translates to differential MHC-presented peptide epitopes, the most common form of which is simple sequence polymorphisms. The universe of potential minor H antigens is large when transplantation is performed between genetically unrelated, MHC-matched individuals, especially considering the remarkable discriminative sensitivity of T cells. However, the phenomenon of immunodominance greatly simplifies immune responses that ensue. One mouse minor H antigen, H60, stands out in that the preponderance of the CD8 T cell response elicited in a complex alloantigenic setting is directed against this single minor H antigen epitope. Its immunodominance is because mice lacking H60 develop an unusually robust T cell repertoire dedicated to this single minor H antigen. The now well-characterized mouse minor H antigen system should provide a vehicle to assess the degree to which immunodominant alloantigens contribute to transplant rejection.
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minor Histocompatibility antigens
Current Opinion in Immunology, 1997Co-Authors: Elizabeth Simpson, Derry C RoopenianAbstract:The existence of transplantation antigens, in addition to those encoded by genes in the MHC, has been known for over half a century. The molecular identification of these additional minor Histocompatibility (H) antigens lagged behind that of their MHC counterparts, largely because minor H antigens are recognised by T cells and not by antibodies. In the past year, however, new minor H antigens have been identified at both the genetic and protein level and include Uty, a second novel gene encoding a male-specific epitope in mice, a novel autosomal gene encoding each of the H-13 alleles of mice, and a second male-specific epitope encoded by the SMCY gene.
Anthony W De Tomaso - One of the best experts on this subject based on the ideXlab platform.
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the fester locus in botryllus schlosseri experiences selection
BMC Evolutionary Biology, 2012Co-Authors: Marie L. Nydam, Anthony W De TomasoAbstract:Background Allorecognition, the ability of an organism to distinguish self from non-self, occurs throughout the entire tree of life. Despite the prevalence and importance of allorecognition systems, the genetic basis of allorecognition has rarely been characterized outside the well-known MHC (Major Histocompatibility Complex) in vertebrates and SI (Self-Incompatibility) in plants. Where loci have been identified, their evolutionary history is an open question. We have previously identified the genes involved in self/non-self recognition in the colonial ascidian Botryllus schlosseri, and we can now begin to investigate their evolution. In B. schlosseri, colonies sharing 1 or more alleles of a gene called FuHC (Fusion Histocompatibility) will fuse. Protein products of a locus called fester, located ~300 kb from FuHC, have been shown to play multiple roles in the Histocompatibility reaction, as activating and/or inhibitory receptors. We test whether the proteins encoded by this locus are evolving neutrally or are experiencing balancing, directional, or purifying selection.
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fester a candidate allorecognition receptor from a primitive chordate
Immunity, 2006Co-Authors: Spencer V Nyholm, Ayelet Voskoboynik, Emmanuelle Passegue, William B Ludington, Katrina Mitchel, Irving L Weissman, Anthony W De TomasoAbstract:Summary Histocompatibility in the primitive chordate, Botryllus schlosseri , is controlled by a single, highly polymorphic locus, the FuHC . By taking a forward genetic approach, we have identified a locus encoded near the FuHC , called fester , which is polymorphic, polygenic, and inherited in distinct haplotypes. Somatic diversification occurs through extensive alternative splicing, with each individual expressing a unique repertoire of splice forms, both membrane bound and potentially secreted, all expressed in tissues intimately associated with Histocompatibility. Functional studies, via both siRNA-mediated knockdown and direct blocking by monoclonal antibodies raised against fester , were able to disrupt predicted Histocompatibility outcomes. The genetic and somatic diversity, coupled to the expression and functional data, suggests that fester is a receptor involved in Histocompatibility.
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isolation and characterization of a protochordate Histocompatibility locus
Nature, 2005Co-Authors: Anthony W De Tomaso, Spencer V Nyholm, William B Ludington, Katrina Mitchel, Katherine J. Ishizuka, Karla J. Palmeri, Irving L WeissmanAbstract:Histocompatibility—the ability of an organism to distinguish its own cells and tissue from those of another—is a universal phenomenon in the Metazoa. In vertebrates, Histocompatibility is a function of the immune system controlled by a highly polymorphic major Histocompatibility complex (MHC), which encodes proteins that target foreign molecules for immune cell recognition. The association of the MHC and immune function suggests an evolutionary relationship between metazoan Histocompatibility and the origins of vertebrate immunity. However, the MHC of vertebrates is the only functionally characterized Histocompatibility system; the mechanisms underlying this process in non-vertebrates are unknown. A primitive chordate, the ascidian Botryllus schlosseri, also undergoes a Histocompatibility reaction controlled by a highly polymorphic locus. Here we describe the isolation of a candidate gene encoding an immunoglobulin superfamily member that, by itself, predicts the outcome of Histocompatibility reactions. This is the first non-vertebrate Histocompatibility gene described, and may provide insights into the evolution of vertebrate adaptive immunity. The rejection of transplanted tissues is a puzzling phenomenon; it can be explained as a necessary evil of immune system function, but it could also be an evolutionary relic or a real function that we do not understand. The discovery of the first known non-vertebrate Histocompatibility locus suggests that there is some truth in at least two of these suggestions. Colonies of the colonial sea-squirt Botryllus schlosseri that make contact either reject each other or undergo a natural transplantation reaction to produce a chimaera, depending on which version of a polymorphic gene called FuHC is present. It is the product of this gene that has now been found to be a member of the immunoglobulin family, similar to the major Histocompatibility complex that encodes the proteins that target foreign molecules for immune cell recognition in vertebrates.
Stanley R Riddell - One of the best experts on this subject based on the ideXlab platform.
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An antigen produced by splicing of noncontiguous peptides in the reverse order
2016Co-Authors: Edus H Warren, Nathalie J. Vigneron, Marc A. Gavin, Pierre G. Coulie, Vincent Stroobant, Re Dalet, Scott S. Tykodi, Suzanne M. Xuereb, Jeffrey K. Mito, Stanley R RiddellAbstract:CD8-positive T lymphocytes recognize peptides that are usually derived from the degradation of cellular proteins and are presented by class I molecules of the major Histocompatibility complex. Here we describe a human minor Histocompatibility antigen created by a polymorphism in the SP110 nuclear phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in the predicted SP110 protein. The antigenic peptide could be produced in vitro by incubation of precursor peptides with highly purified 20S proteasomes. Cutting and splicing probably occur within the proteasome by transpeptidation. M ost nucleated cells display on their surface a broad repertoire of peptides derived from proteasome-mediated degradation of intracellular proteins and bound to major Histocompatibility complex (MHC) class I molecules, which are known in human
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a single minor Histocompatibility antigen encoded by ugt2b17 and presented by human leukocyte antigen a 2902 and b 4403
Transplantation, 2007Co-Authors: Seitaro Terakura, Makoto Murata, Edus H Warren, Alessandro Sette, John Sidney, Tomoki Naoe, Stanley R RiddellAbstract:Background. T-cell responses to minor Histocompatibility antigens are mediators of graft-versus-host disease and organ graft rejection. We previously identified a human minor Histocompatibility antigen that is recognized by CD8+ cytotoxic T lymphocytes (CTLs) and encoded by the UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17) gene, which is highly expressed in the liver, colon, and small intestine. The UGT2B17 is presented by human leukocyte antigen (HLA)-A*2902, and the immunogenicity of this minor Histocompatibility antigen results from differential protein expression in donor and recipient cells as a consequence of a UGT2B17 gene deletion. Methods. An HLA-B*4403-restricted CD8+ CTL clone was isolated from the same hematopoietic stem cell transplant recipient that exhibited an HLA-A*2902-restricted UGT2B17-specific response. The minor Histocompatibility antigen recognized by the HLA-B*4403-restricted clone was identified, and the ability of the peptide to be presented by HLA-B*4402 was examined. Results. The HLA-B*4403-restricted CTL clone recognized a peptide encoded by UGT2B17, which is identical to the peptide presented by HLA-A*2902. Peptide binding assays revealed this UGT2B17 peptide binds with comparable affinity to HLA-B*4402 as to HLA-B*4403. This patient had acute graft-versus-host disease involving liver and gastrointestinal tract, suggesting the T-cell response directed against UGT2B17 is involved in graft-versus-host disease. Conclusions. A single peptide encoded by UGT2B17 can be presented by HLA-A*2902, B*4402 and B*4403, and may serve as an immunodominant minor Histocompatibility antigen in individuals with these HLA alleles that undergo transplantation of stem cells or organ grafts from UGT2B17 disparate donors.
