Search results for "Histocompatibility"

OP0204 Autophagy and Unfolded Protein Response: A Fine Balance that can Influence the Pathogenesis of Ankylosing Spondylitis and Inflammatory Bowel D…

2015

Background We have shown an increase in the unfolded protein response (UPR) with decreased ERAP1 or ERAP2 function in an in vitro system. Similarly UPR has been demonstrated to correlate with onset of disease in the HLA-B27 rat model. UPR has been difficult to demonstrate in the gut of AS patients but autophagy is upregulated. ERAP2 is associated with both AS and inflammatory bowel disease (IBD). Objectives Here we explore the moderating effect of autophagy on UPR. Specifically we study the impact of suppressing autophagy on UPR. Methods Lamina Propria Mononuclear cells (LPMC) were isolated from terminal ileal biopsies of 10 AS patients. Autophagy was suppressed with 2 agents anisomycin and…

Distinct bhaplotype structure at the innate immune receptor Toll-like receptor 2 across bank vole populations and lineages in Europe

2015

Abstract: Parasite-mediated selection may contribute to the maintenance of genetic variation at host immune genes over long time scales. To date, the best evidence for the long-term maintenance of immunogenetic variation in natural populations comes from studies on the major histocompatibility complex (MHC) genes, whereas evidence for such processes from other immune genes remains scarce. In the present study, we show that, despite pronounced population differentiation and the occurrence of numerous private alleles within populations, the innate immune gene Toll-like receptor 2 (TLR2) displays a distinct haplotype structure in 21 bank vole (Myodes glareolus) populations across Europe. Haplo…

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…