Search results for "Minor histocompatibility antigen"

Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma

2007

Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3-/- mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD1…

Enhancement of Antigen Presentation by Deletion of Viral Immune Evasion Genes Prevents Lethal Cytomegalovirus Disease in Minor Histocompatibility Ant…

2020

Hematoablative treatment followed by hematopoietic cell transplantation (HCT) for reconstituting the co-ablated immune system is a therapeutic option to cure aggressive forms of hematopoietic malignancies. In cases of family donors or unrelated donors, immunogenetic mismatches in major histocompatibility complex (MHC) and/or minor histocompatibility (minor-H) loci are unavoidable and bear a risk of graft-vs.-host reaction and disease (GvHR/D). Transient immunodeficiency inherent to the HCT protocol favors a productive reactivation of latent cytomegalovirus (CMV) that can result in multiple-organ CMV disease. In addition, there exists evidence from a mouse model of MHC class-I-mismatched GvH…

A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

2019

Background Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K arra…

µ-Calpain conversion of antiapoptotic Bfl-1 (BCL2A1) into a prodeath factor reveals two distinct alpha-helices inducing mitochondria-mediated apoptos…

2011

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c r…

Rapid identification of minor histocompatibility antigen HA-1 subtypes H and R using fluorescence-labeled oligonucleotides

2000

Acknowledgments: We thank Brigitte Schuch and Karola Schmidt for excellent technical assistance. This work was supported by a grant of the Deutsche Krebshilfe (Nr. 70-2427 and Nr. 70-2428). Abstract: Donor-recipient disparitiy of the minor histocompatibility antigen HA-1 is relevant for the development of graft-versus-host disease after HLA-matched sibling allogeneic bone marrow transplantation in HLA-A*0201-positive individuals. Two different alleles of HA-1 with a single amino acid polymorphism have been identified. Here we describe a time- and cost-efficient method for HA-1 typing of genomic DNA, using site-specific hybridization probes with the LightCycler. This method was compared with…

Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis

2014

The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27(+) but not HLA-B27(-) AS patients or controls. Forty-nine AS cases and 22 healthy…

EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation

2005

Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1…

Depletion of Alloreactive Donor T Lymphocytes by CD95-Mediated Activation-Induced Cell Death Retains Antileukemic, Antiviral, and Immunoregulatory T …

2007

In allogeneic hematopoietic stem cell transplantation (AHSCT) graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect are closely but not invariably linked. Thus, harnessing donor lymphocyte mediated GVL immunity and separating it from GVHD is of particular interest. Based on results obtained in murine models we have explored the CD95-mediated activation-induced cell death (AICD) strategy to selectively deplete alloreactivity in human donor T lymphocytes in vitro. Following stimulation of CD3(+) T cells isolated from HLA-A* 0201-positive donors with HLA or minor histocompatibility antigen mismatched hematopoietic or nonhematopoietic cells in the presence of agonistic anti-CD…

Major Histocompatibility Complex Modulation and Loss

2002

Consequence of Histoincompatibility beyond GvH-Reaction in Cytomegalovirus Disease Associated with Allogeneic Hematopoietic Cell Transplantation: Cha…

2021

Hematopoietic cell (HC) transplantation (HCT) is the last resort to cure hematopoietic malignancies that are refractory to standard therapies. Hematoablative treatment aims at wiping out tumor cells as completely as possible to avoid leukemia/lymphoma relapse. This treatment inevitably co-depletes cells of hematopoietic cell lineages, including differentiated cells that constitute the immune system. HCT reconstitutes hematopoiesis and thus, eventually, also antiviral effector cells. In cases of an unrelated donor, that is, in allogeneic HCT, HLA-matching is performed to minimize the risk of graft-versus-host reaction and disease (GvHR/D), but a mismatch in minor histocompatibility antigens …