• Risk factors for development of acute graft-versus-host disease depend upon the type of graft you're using-whether it's from an HLA [human leukocyte antigen]-matched sibling versus an HLA-matched unrelated donor, or if you're using a partially matched donor. (targetedonc.com)
  • Long-term engraftment of allogeneic cells necessitates eluding immune-mediated rejection, which is currently achieved by matching for human leukocyte antigen (HLA) expression, immunosuppression, and/or delivery of donor-derived cells to sanctuary sites. (ashpublications.org)
  • The human leukocyte antigen (HLA) system is fundamental to transplant biology. (mhmedical.com)
  • The graft usually comes from a human leukocyte antigen (HLA)-matched donor and contains hematopoietic cells as well as immune cells, including T lymphocytes. (gvhdhub.com)
  • We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. (cdc.gov)
  • 13 Our study substantially expands this work by not only analysing imputed classical human leukocyte antigen (HLA) alleles, but also examining variant HLA amino-acid positions in conjunction with single-nucleotide polymorphism (SNP) genotypes across the extended MHC region (chromosome 6: 26-34 Mb). (cdc.gov)
  • However, there is death by apoptosis of thymocytes that do not interact with MHC molecules or have high-affinity receptors for self MHC plus self antigen a process referred to as negative selection. (wikipedia.org)
  • The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. (fujita-hu.ac.jp)
  • These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (∼100 per cell), while they could respond at cytokine production level. (fujita-hu.ac.jp)
  • Besides the secretion of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), the increased expression of receptor repertoire (pattern recognition receptors, PRR) on APCs, mostly macrophages and dendritic cells, occurs as a result of the release of endogenous and exogenous antigens (damage-associated molecular patterns, DAMPs, and pathogen-associated molecular patterns, PAMPs). (hindawi.com)
  • Although graft or bone marrow rejection can have detrimental effects, there are immunotherapy benefits when cytotoxic T lymphocytes are specific for a self antigen and can target antigens expressed selectively on leukemic cells in order to destroy these tumor cells referred to as graft-versus- leukemia effect (GVL). (wikipedia.org)
  • Cytotoxic T lymphocytes were determined as the cellular effectors of GVHD, and the key role of antigen-presenting cells (APCs) in T-lymphocyte activation was established during the following years [ 11 , 12 ]. (hindawi.com)
  • Although human CD20 has previously been described as functional selection marker and suicide gene after retroviral transfer to T lymphocytes, 9 , 10 the specificities of these T cells were unknown, and therefore a potential effect of CD20 on antigen-specific T-cell functions could not be investigated. (haematologica.org)
  • The recipient developed GVHD despite having a HLA- matched genes at the Major Histocompatibility locus. (wikipedia.org)
  • Some of these antigens are ubiquitously expressed in nucleated male cells, and the presence of these antigens has been associated with a greater risk of developing GVHD allogeneic stem cell transplantation for a HLA matched gene when there's a male recipient and female donor. (wikipedia.org)
  • The histocompatibility differences between the donor and the recipient, the presence of donor's immunocompetent cells, and the inability of the recipient to reject these cells were defined as the basic pathogenic prerequisites for GVHD development by Billingham in 1966 [ 10 ]. (hindawi.com)
  • Donor T cells may also induce GvHD due to recognition of allo-antigens on non-malignant tissues of the patient. (haematologica.org)
  • Minor histocompatibility antigen differences likely account for GVHD in HLA-identical sibling stem cell transplants. (unboundmedicine.com)
  • However, even in a fully HLA matched HCT, GVHD still occurs due to donor T cells directed against minor histocompatibility antigens (MiHAs), polymorphic peptides displayed on host HLA molecules. (mhmedical.com)
  • This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. (wikipedia.org)
  • MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells. (wikipedia.org)
  • The lack of recognition of a T cell to this self antigen is the reason why allogeneic stem cell transplantation for an HLA matched gene or a developing fetus's MiHAs during pregnancy may not be recognized by T cells and marked as foreign leading to an immune response. (wikipedia.org)
  • Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). (fujita-hu.ac.jp)
  • 100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. (fujita-hu.ac.jp)
  • The roles of antigen-specificity, responsiveness to TGFβ and APC subsets in tumour-induced expansion of regulatory T cells. (imperial.ac.uk)
  • The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. (haematologica.org)
  • 1 , 2 The anti-tumor effect of DLI is mediated by donor T cells recognizing allo-antigens on the malignant cells of the recipient. (haematologica.org)
  • T-cell receptor (TCR) gene transfer is an attractive strategy for rapid in vitro generation of high numbers of antigen specific T cells. (haematologica.org)
  • 4 In addition, TCRs for minor histocompatibility antigens, including HA-1 and HA-2, have been transferred to donor-derived virus-specific T cells to treat patients with hematologic malignancies after allogeneic stem cell transplantation. (haematologica.org)
  • Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease. (google.ca)
  • Here, we show that even expression of minor histocompatibility (mH) antigens is sufficient to provoke acute rejection of tissues differentiated from ES cells. (ox.ac.uk)
  • This propensity for tolerance could be attributed to the paucity of professional antigen-presenting cells and the expression of transforming growth factor (TGF)-?2. (ox.ac.uk)
  • Therefore, the immune cells that are passively transferred in the stem cell graft are more primed against these minor histocompatibility antigens that are known to be associated with the development of acute graft-versus-host disease. (targetedonc.com)
  • or actively by prior immunization of the recipient with graft antigens which evoke specific antibodies and form antigen-antibody complexes which bind to the antigen receptor sites of the T-cells and block their cytotoxic activity. (lookformedical.com)
  • In situ dissection of the graft-versus-host activities of cytotoxic T cells for minor histocompatibility antigens. (alcyomics.com)
  • The implication of these results would be that myeloma-specific T cell subfamilies might be positively selected from the donor inoculum and infused to myeloma patients post ASCT, to afford separation of allo- from tumor-reactive T cells without the prior need to define specific target antigens. (biomedcentral.com)
  • A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. (elevate.bio)
  • TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. (elevate.bio)
  • Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. (elevate.bio)
  • These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the body's immune system to respond to fight off and kill the tumor cells. (elevate.bio)
  • Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patient's native cells, and not by the cells from the stem cell transplant donor. (elevate.bio)
  • The target of TSC-100 is the minor histocompatibility antigen HA-1, which is a lineage-specific antigen found on blood cells. (tscan.com)
  • La primera publicación de Galadriel Mirkwood fue titulada " In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type "² ( Matzinger & Mirkwood , 1978), aunque a diferencia de Hetherington, Matizinger fue baneada de la revista "Journal of Experimental Medicine" debido a su inusual coautora. (nabbublog.cl)
  • Galadriel Mirkwood's first publication was titled " In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type " ( Matzinger & Mirkwood , 1978), although unlike Hetherington, Matizinger was banned from the journal "Journal of Experimental Medicine" due to its unusual co-author. (nabbublog.cl)
  • In phase I, chemotherapy or radiotherapy as part of transplant conditioning causes host tissue damage and release of inflammatory cytokines such as TNF-α, IL-1, and IL-6, with resulting priming of host antigen-presenting cells (APCs). (mhmedical.com)
  • DC can acquire and process antigens in the periphery before maturing and migrating to secondary lymphoid tissues where they present the antigens and deliver co-stimulatory signals to T cells. (ox.ac.uk)
  • Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population restricted by the non-polymorphic, major histocompatibility complex class I-related protein 1, MR1. (ox.ac.uk)
  • The recognition of a mature T cell to this self antigen should not induce an immune response. (wikipedia.org)
  • Absence of a costimulatory signal results in T-cell anergy, which is a key mechanism of peripheral immune tolerance to self-antigen in normal immunoregulation. (mhmedical.com)
  • To test for linked suppression, animals were transplanted with a second graft-bearing tolerated and third party antigens. (ox.ac.uk)
  • Splenocytes from these and control tolerant animals when transferred into partially immunocompromised Fas mutant or control recipients, induced antigen-specific suppression of graft rejection. (ox.ac.uk)
  • Concurrent with its use for shared antigens, BlueSphere is deploying TCXpress™ and NEOXpress™, a proprietary patient-specific neoantigen discovery platform, to develop its TCX-201 Program, which aims to identify TCRs reactive against patient-specific neoantigens. (bluespherebio.com)
  • We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and β2- microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. (fujita-hu.ac.jp)
  • Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance. (imperial.ac.uk)
  • METHODS: Tolerance to transplanted skin and bone marrow, mismatched for multiple minor histocompatibility antigens, was induced in Fas mutant and control mice using anti-CD4 and anti-CD8 monoclonal antibodies. (ox.ac.uk)
  • RESULTS: Monoclonal antibody therapy rendered Fas mutant mice tolerant of minor disparate skin and bone marrow. (ox.ac.uk)
  • Additionally, tolerant Fas mutant mice accepted grafts bearing tolerated and third party antigens. (ox.ac.uk)
  • The major focus of the Department of Immunology is on Translational Immunology and its spectrum of basic research covers T cell biology, antibodies, antigen presentation and innate immunity. (immunology-tuebingen.de)
  • Our identification of the first non-human primate-specific minor histocompatibility antigen now published at Frontiers in Immunology. (wisc.edu)
  • Even when a transplant donor and recipient are identical with respect to their major histocompatibility complex genes, the amino acid differences in minor proteins can cause the grafted tissue to be slowly rejected. (wikipedia.org)
  • H-Y antigens are encoded by genes on the Y chromosome. (wikipedia.org)
  • 12 - 15 These studies focused mainly on major histocompatibility complex (MHC) class II genes, and found evidence that class II alleles such as HLA-DRB1*03:01 are associated with auto-antibody production. (cdc.gov)
  • Kelly Olsen defended her doctoral dissertation, Shared Minor Histocompatibility Antigen Discovery and Targeting in the Context of Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies. (unc.edu)
  • An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. (lookformedical.com)
  • The prognosis for leukemia patients who've relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse," said Elizabeth Krakow, M.D., MSc. (elevate.bio)
  • H60 is a minor histocompatibility antigen for which the specific CD8 T-cell response dominates during alloresponse after MHC-matched allogeneic transplantation. (molcells.org)
  • BSB-1001, targeting the minor histocompatibility antigen-1 (HA-1) and part of BlueSphere's TCX-101 Program, is the first TCR-T cell therapy candidate generated using TCXpress and is in development for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS) in conjunction with allogeneic hematopoietic stem cell transplantation (alloSCT). (bluespherebio.com)
  • These antigens include organic dusts containing bacteria, fungi,4 animal or plant proteins, or low-molecular-weight chemicals. (cdc.gov)
  • About 12 days after LPC-1, a myeloma tumor, was transplanted it became resistant to lysis by allogenic CTL (anti-H-2(d)) and by CTL directed to trinitrophenyl groups or minor histocompatibility antigens. (elsevierpure.com)
  • However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. (elevate.bio)
  • Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains. (lookformedical.com)
  • Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (lookformedical.com)
  • The response was CD4 help-depen-dent, demonstrating the potency of H60H as a cellular antigen. (molcells.org)
  • The response induced by the H60H cellular antigen was comparable to that induced by H60 in its peak magnitude and overall immune kinetics. (molcells.org)
  • Twenty-three female UCB samples were collected from healthy mothers and analyzed for minor histocompatibility Ag HY-specific responses. (ashpublications.org)
  • It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. (lookformedical.com)
  • TSC-101 is targeted to the lineage-specific blood cell antigen HA-2, which is a novel target for cell therapy. (tscan.com)
  • The Endoplasmic Reticulum Aminopeptidase 1 and 2 (ERAP1 and ERAP2) and Insulin Regulated Aminopeptidase (IRAP) are three M1 zinc metalloproteases whose role in antigen processing is the refining of peptidome either in the Endoplasmic reticulum (ERAP1 and ERAP2), or in the endosomes (IRAP). (uniroma1.it)
  • Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. (cdc.gov)
  • Clinically, the number and size of the ulcers are the two main criteria used to divide ulcers into three forms: minor, major, and herpetiform. (medscape.com)
  • In contrast, complex aphthosis has a severe clinical course, with an almost continuous presence of minor or major ulcers. (medscape.com)
  • Microvascular disease may also impair skin healing, so that even minor breaks in skin integrity can develop into deeper ulcers and easily become infected, particularly in the lower extremities. (msdmanuals.com)
  • In general, there are few lesions of the minor or herpetiform form. (medscape.com)
  • Minor aphthous ulcer: Small superficial oval erosions with yellow pseudomembrane and an erythematous border are evident on the labial aspect of the left lower lip. (medscape.com)