Search results for "Histocompatibility"

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…

Phenotype, Function, and Safety of a p53 TCR Bicistronic GMP-Suitable Retroviral Construct.

2006

Abstract Malignant transformation of normal cells is frequently correlated with the involvement of so called tumor-associated antigens (TAA). Such proteins, that are often overexpressed in tumor cells, can be recognized by cytotoxic CD8+ T cells (CTL) if presented as peptides on MHC (Major-Histocompatibility-Complex)-class I molecules. Due to self-tolerance mechanisms, the peripheral T cell repertoire is devoid of efficient TAA-specific, tumor-reactive CTL with high affinity, limiting the successful development of antigen-specific immunotherapeutic strategies based on such tumor-reactive T cells. The aim of this project is the preclinical development of an adoptive immunotherapy against p53…

p53 Immunotherapy of Cancer

2012

Mutation and overexpression of the p53 tumor suppressor protein are the most common genetic alterations in human cancers. Peptides derived from non-mutated (wild type, wt) and mutated p53-molecules, processed and presented in the context of major histocompatibility complex (MHC) molecules by tumor cells for T-cell recognition, could serve as broad targets for cancer immunotherapy. Isolating p53-reactive T lymphocytes in healthy donors or patients has been hampered by the fact that most individuals display a peripheral p53-reactive T-cell repertoire that is devoid of high-avidity MHC class I-restricted cytotoxic T lymphocytes (CTL). Only low-avidity T lymphocytes are left due to self-toleran…

The clinical utility of PGD with HLA matching: a collaborative multi-centre ESHRE study

2018

Study question Has PGD-HLA been successful relative to diagnostic and clinical efficacy? Summary answer The diagnostic efficacy of PGD-HLA protocols was found lower in this study in comparison to published PGD-HLA protocols and to that reported for general PGD by ESHRE (78.5 vs 94.1% and vs 92.6%, respectively), while the clinical efficacy has proven very difficult to assess due to inadequate follow-up of both the ART/PGD and HSCT procedure outcomes. What is known already The first clinical cases for PGD-HLA were reported in 2001. It is now a well-established procedure, with an increasing number of cycles performed every year. However, PGD-HLA is still offered by relatively few PGD centres,…

Loss of interferon-gamma inducibility of the MHC class II antigen processing pathway in head and neck cancer: evidence for post-transcriptional as we…

2008

Summary Background  Abnormalities of the major histocompatibility complex (MHC) antigens by tumour cells impair the cellular immune response and promote tumour evasion from immune surveillance. So far, studies analysing the MHC class II expression levels in head and neck cancer have been limited. Objectives  Therefore, we investigated the constitutive and interferon (IFN)-γ-regulated expression profiles of MHC class II antigen processing machinery (APM) in various head and neck cancer cell lines and also analysed the MHC class II expression in head and neck cancer lesions. Methods  Using immunohistochemistry, flow cytometry, and reverse transcriptase-polymerase chain reaction analyses we in…

CD4+ and CD8+ clonal T cell expansions indicate a role of antigens in ankylosing spondylitis; a study in HLA-B27+ monozygotic twins.

2001

SUMMARYAnkylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether the T cell repertoires of individuals with AS show signs of increased stimulation by exogenous antigens, CD4+ and CD8+ T cell subsets of five monozygotic HLA-B27+ twins (two concordant and three discordant for AS) and CD8+ T cell repertoires of three healthy HLA-B27+ individuals were characterized by TCR β-chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR3 spectra were further analysed by BJ-segment analysis and TCRB-CDR3 from expanded T cell clones were sequenced. In an analysis of all data (519/598 possible TCRB-CDR3 spectra), AS …

Lysis of human pancreatic adenocarcinoma cells by autologous HLA-class I-restricted cytolytic T-lymphocyte (CTL) clones.

1993

From the primary site of a pancreatic adenocarcinoma (patient BE) a permanent cell line (MZ-PC-2) was established in tissue culture. In the course of mixed lymphocyte-tumor-cell cultures (MLTC) with autologous blood-derived lymphocytes, we isolated CTL clones that lysed autologous tumor cells but not autologous EBV-transformed B cells (EBV-B) and not K562. Pre-treatment of MZ-PC-2 cells with IFN-gamma was required to obtain significant lysis in 4-hr cytotoxicity assays. IFN-gamma was superior to IFN-alpha in that respect. Among MLTC responder lymphocytes, tumor-reactive CTL proliferated more strongly in response to MZ-PC-2 cells treated with IFN-gamma than to untreated tumor cells. Three CT…

Antibodies to vascular endothelial cells in chronic rejection of renal allografts.

2000

MHC-unrestricted recognition of bacteria-infected target cells by human CD8+ cytotoxic T lymphocytes.

1992

Abstract A CD8 + αβTCR + T cell clone (A35) was isolated from the synovial fluid of a patient with postenteric reactive arthritis caused by Yersinia enterocolitica . This clone efficiently killed autologous and allogeneic target cells that had been preincubated with live but not with heat-killed bacteria. There was no restriction by polymorphic parts of HLA-A, -B. or -C molecules and a HLA class II-deficient mutant cell line was lysed as efficiently as its normal counterpart, whereas infected HLA class I-deficient cells (Daudi cells) were not. The clone showed crossreaction between Yersinia enterocolitica , Escherichia coli , Pseudomonas aeruginosa , and Streptococcus pyogenes , but did not…

16thIHIW: Anti-HLA alloantibodies of the of IgA isotype in re-transplant candidates

2012

Summary In this multicentre study, sera from 803 retransplant candidates, including 775 kidney transplant recipients, were analysed with regard to the presence and specificity of anti-HLA alloantibodies of the IgA isotype using a modified microsphere-based platform. Of the kidney recipients, nearly one-third (n = 237, 31%) had IgA alloantibodies. Mostly, these antibodies were found in sera that also harboured IgG alloantibodies that could be found in a total of 572 (74%) of patients. Interestingly, IgA anti-HLA antibodies were preferentially targeting HLA class I antigens in contrast to those of the IgG isotype, which targeted mostly both HLA class I and II antigens. Donor specificity of th…