Search results for "major histocompatibility complex"

Major Histocompatibility Complex Modulation and Loss

2002

Murine Model of Cytomegalovirus Latency and Reactivation

2008

Efficient resolution of acute cytopathogenic cytomegalovirus infection through innate and adaptive host immune mechanisms is followed by lifelong maintenance of the viral genome in host tissues in a state of replicative latency, which is interrupted by episodes of virus reactivation for transmission. The establishment of latency is the result of aeons of co-evolution of cytomegaloviruses and their respective host species. Genetic adaptation of a particular cytomegalovirus to its specific host is reflected by private gene families not found in other members of the cytomegalovirus group, whereas basic functions of the viral replicative cycle are encoded by public gene families shared between …

Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes

1989

Based on evidence of an increased rate of respiratory infections in sudden infant death (SID) infants as well as the observation of familial occurrence, we analysed in a retrospective study class II and class II genes of the major histocompatibility complex in 40 cases of SID by Southern blot analysis of DNA obtained post mortem from tissue samples. In 24 cases, the parents were interviewed and confirmatory human lymphocyte antigen (HLA) and DNA typing was carried out. Using HLA-DR beta and -DQ beta probes, no evidence of an abnormal HLA-DR frequency distribution in SID infants was detected (P = 0.97). Using DNA probes for the tandemly arranged complement C4 and steroid 21-hydroxylase genes…

Coordinate downregulation of multiple MHC class I antigen processing genes in chemical-induced murine tumor cell lines of distinct origin

2000

In murine tumor cell lines, downregulation of MHC class I surface expression has been frequently detected, but the underlying molecular mechanisms of such deficiencies have not been defined. In this study, murine tumor cell lines of different histology derived from spontaneous or from chemical-induced tumors were analyzed for the expression of multiple components of the major histocompatibility complex (MHC) class I antigen-processing machinery (APM), including the peptide transporter TAP, the interferon (IFN)-gamma inducible proteasome subunits and several chaperones. The tumor cell lines analyzed demonstrated a heterogeneous expression pattern of various APM components. In comparison to c…

Fuch's heterochromic cyclitis and HLA histocompatibility antigens

1994

Genetic typing of class I major histocompatibility complex (MHC) antigens (HLA-A, -B and -C) was performed in 22 patients with Fuch's heterochromic cyclitis (FHC) and in a control group of 339 healthy subjects in order to ascertain whether there are any genetic factors that protect against or increase the risk of developing this disease. The frequency of only one HLA-antigen was found to differ significantly in the patients with FHC as compared with the normal subjects: HLA-A2 had a negative association with FHC (9.09% in FHC versus 47.47% in the control group; p<0.01, Fisher's exact test with correction for the number of antigens studied) with an odds ratio of 0.11 (95% confidence limits 0…

Towards Adoptive Immunotherapy Using High Affinity T Cell Receptors

2003

The hdm2 oncoprotein is frequently overexpressed in a variety of human malignancies, including acute myeloid and lymphoblastic leukemia. Synthetic peptides representative of hdm2 sequences were tested for their binding to A2.1. HLA-A2.1. (/Kb)-Tg mice were immunized with A2.1-binding hdm2 peptides in order to induce A2.1-restricted and hdm2-specific CTL. A2.1-restricted CTL lines obtained from both A2.1 and HuCD8 × A2.1/Kb-Tg mice were able to recognize a synthetic 8-mer peptide representative of a N-terminal hdm2 sequence. These CTL were capable of recognizing and lysing Saos-2 cells transfected with the hdm2 gene as opposed to the parental cell line that lacks any detectable hdm2 expressi…

Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination

2019

AbstractViral escape from CD8+cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8+T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, t…

Analysis of Invariant Chain Processing in 3 Day Cultured Rat Langerhans Cells

1995

MHC class II molecules, critical peptide binding elements involved in the presentation of exogenous antigen to T helper cells, are expressed constitutively by Langerhans cells (LC) within their epidermal microenvironment. Several studies in mouse and man demonstrated, that short term in vitro culture of LC entails remarkable functional and penotypic alterations, including a profound increase of class II elements exposed at the LC’s surface1. Biosynthetic analysis revealed a downregulation of class II synthesis during the culture period2,3. In recent work on rat LC we described the uncoupling of the coordinately regulated biosynthesis of class II and invariant chain proteins in the course of…

Editorial: Understanding Gamma Delta T Cell Multifunctionality - Towards Immunotherapeutic Applications.

2020

Introduction: gd T cells have been characterized by the expression of a gd T cell receptor (TCR).When the gd TCR and the corresponding ab TCR were first discovered it was assumed that the corresponding cell types were likely to be functionally very similar. However, some 30 years later, we have realized that they are not. Unlike ab T cells, gd T cells (i) sense target antigens independent of MHC molecules; (ii) display NK-cell like innate reactivities, including killing of infected cells as well as microbes; (iii) are able to take up large particulates, including bacteria, and (iv) can act as professional antigen presenting cells. The “stress sensing” abilities of gd T cells have led to a g…

Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.

2018

Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261. Moreover, SB28 shows features of a poorly immunogenic tumor, with low MHC-I expression and modest CD8(+) T-cell infiltration, suggest…