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Lymphocyte surface marker expression in rheumatic diseases: evidence for prior activation of lymphocytes in vivo.

Expression of major histocompatibility complex (MHC) class II and other lymphocyte activation markers on peripheral blood and synovial fluid T lymphocytes from patients with rheumatoid arthritis (RA), psoriatic arthritis, and Reiter's syndrome were measured and the mean fluorescence intensities of these antigens were assessed. Increased expression of MHC class II antigens of synovial fluid T lymphocytes is not unique to RA, though it is quantitatively greater on RA synovial fluid T cells. There was less expression of other lymphocyte activation markers (4F2, transferin receptor) and a marked d…

Characteristics of a human liver allograft--derived T-cell line that exhibits suppressor activity.

In an attempt to identify predominant cell populations that may mediate liver allograft dysfunction, the phenotypic and functional character … temperature. The suppressive activity of JB cells and supernatants was not alloantigen-specific or major histocompatibility complex-restricted, did not shift mixed lymphocyte reaction kinetics, and was capable of inhibiting in vitro stimulation of peripheral blood lymphocytes in mixed lymphocyte reaction only when presented early in the culture. These findings provide the first …

Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity.

Mice were infected with Listeria monocytogenes and Lyt-2+ T cell clones capable of lysing Ag-primed bone marrow macrophages were established. In accordance with earlier findings obtained at the population level, some T cell clones were identified which lysed bone marrow macrophages of different MHC type provided the relevant Ag was present. This unusual target cell recognition was further analyzed using a T3+, L3T4-, Lyt-2+, F23+, KJ16+ T cell clone, designated L-28. Target cell lysis by this clone was Ag specific, apparently non-MHC restricted. In contrast, YAC cells and P815 cells were not l

Cytogenetic studies in Wiskott-Aldrich syndrome: identification of a case with a 6p chromosome abnormality.

Lymphocytes from patients with Wiskott-Aldrich syndrome (WAS) were studied with prometaphase G banding to search for minor chromosome anomalies and in mutagen stress assays to assess the extent of chromosome breakage under these conditions. One patient, a sporadic case of WAS, was found to have a stable inversion of a large segment of one chromosome 6 that involved the region encoding the major histocompatibility complex (MHC). The anomaly was not present in the patient's parents, nor in three other unrelated patients with WAS, all of whom demonstrated X-linked inheritance (based on family his…

Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes.

The frequencies and absolute numbers of B and T cells in the lymphoid organs of five murine strains (NZB, (NZB X NZW)F1, BXSB, MRL/l, and MRL/n) with SLE-like syndromes were examined. We assessed the frequencies of cells bearing surface Ig, C3d and IgG Fc receptors, and theta-antigen. The sequential expression of Ig isotopes on developing B cells and the Ig isotypes expressed on adult B cells were ascertained. In addition, the Ly subsets and the expression of Ia antigens coded for by the I-J subregion of the mouse H-2 complex were examined. Compared to normal, older mice, New Zealand mice had

The relationship between facial annular erythema and anti-SS-A/Ro antibodies in three East Asian women.

A distinct annular erythema developed on the cheeks of three East Asian women who had anti-SS-A/Ro (SSA) antibodies. The erythema was charac … p syndrome and an asymptomatic clinical state. These results are consistent with recent findings of major histocompatibility complex class II expression on target organs in various autoimmune diseases. Based on these findings, erythema appears to represent a broad cutaneous manifestation of these diseases. Furthermore, the presence of SSA antibodies, aberrant HLA-DR expression, a …

The in vitro proliferative response of lymphoid cells of mice infected with Salmonella enteritidis 11RX.

Intraperitoneal injection of (BALB/c x C57BL/6) F1 mice with live, but not killed Salmonella enteritidis 11RX (11RX) induced T cells in the spleen and peritoneal cavity which were able to proliferate in vitro in response to two different forms of 11RX antigens. The majority of cells which proliferated were L3T4+ T cells and most of the response was restricted by the I-A locus of the H-2 major histocompatibility complex, although a smaller K region restricted response was also detected. T cells able to respond to 11RX antigens could only be demonstrated when non-adherent lymphoid cell suspensio…

The genetics of inflammatory bowel disease.

The inflammatory bowel diseases (IBD) comprise complex genetic disorders, with multiple contributing genes. Linkage studies have implicated … IBD genomic regions include IBD2 on chromosome 12q (observed more in UC), and IBD3, containing the major histocompatibility complex region. A short genomic region has been associated with CD on chromosome 5q, but the precise contributing gene is as yet unidentified. The characterization of additional IBD susceptibility genes could potentially lead to the identification of novel …

Cytosolic delivery of bacterial metabolites by riboflavin transporters promotes MR1 antigen presentation and MAIT cell recognition.

Major histocompatibility complex class I-related protein 1 (MR1) presents microbial Vitamin B-related metabolite antigens (VitBAg) at the cell surface to activate mucosal-associated invariant T (MAIT) cells. Precisely how antigen-presenting cells capture these MR1 ligands is not known. Here, we show that the most effective route for presentation of bacterial VitBAg involves passage through the cytosol. Consistent with structural similarities with riboflavin, we find that VitBAg presentation is inhibited by riboflavin. We further show that riboflavin carriers transport VitBAg into cells and enh…

ZNF263-NuRD-mediated repression of STAT1 curtails MHC-I antigen presentation and IFN-γ efficacy in prostate cancer.

Loss of major histocompatibility complex (MHC)-I is a hallmark of prostate cancer (PCa) immune evasion and immunotherapy failure. Here, we identify ZNF263 as a transcriptional repressor that silences MHC-I by recruiting nucleosome-remodeling and deacetylase (NuRD) to the STAT1 promoter, reducing STAT1 and MHC-I expression. Hypoxia enhances this repression through two ZNF263 modifications: phosphorylation-driven phase separation that strengthens NuRD interaction and O-GlcNAcylation at S662 that aids STAT1 promoter binding. O-GlcNAcylation also promotes interaction with protein kinase, DNA‑activ…

A Comprehensive HLA-DR4 MHC Class II Tetramer Platform for the Detection and Functional Validation of Post-Translational Modification Neoantigens.

Post-translational modification (PTM) neoantigens have emerged as key drivers of autoimmune inflammation. However, standardized protocols fo … iated with autoimmune diseases (AUIDs) such as Ankylosing Spondylitis (AS). The platform provides a major histocompatibility complex (MHC) Class II tetramer associated with the PTM neoantigen and integrates modular protein construct, a controllable PTM peptide exchange strategy, and a specific T cell receptor (TCR) validation model. It can be employed to investigate PTM neoantige …

CD74 in hematological malignancies: from MHC chaperone to therapeutic target.

CD74, originally known as the invariant chain of Major Histocompatibility Complex Class II Molecules (MHC class II), has now been acknowledged as a versatile signaling nexus and a universal lymphoma antigen. It has a pivotal role in the maturation, stimulation, and viability of various immune cells, such as B cells, T cells, Regulatory T Cells (Tregs), monocytes, and macrophages. It is extensively and significantly expressed in a variety of hematologic cancers, encompassing acute and chronic leukemias, lymphomas, and multiple myeloma. Given its expression pattern, along with its swift internal…

Mouse orthotopic liver transplantation: Challenges, achievements, and applications.

The surgically challenging mouse orthotopic liver transplant model has provided numerous insights into liver immunobiology, cellular and molecular regulation of liver transplant ischemia-reperfusion injury, liver regeneration, the influence of major histocompatibility complex antigens on transplant outcome, spontaneous transplant tolerance, and regulation of allograft immunity. Nonarterialized and arterialized models have been established. Reduced-size liver transplant models have also been developed and used to determine critical mass and factors that determine tissue injury and regeneration.…

ALS-associated TDP-43 aggregates drive innate and adaptive immune cell activation.

Amyotrophic lateral sclerosis (ALS) is the most common and fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology o … white matter that correlated with phosphorylated TDP-43 accumulation, CD8 T cell infiltration, and major histocompatibility complex expression. Taken together, this study sheds light on a novel cellular response to TDP-43 aggregates through an immunological lens.

Аберрантный метаболизм питательных веществ в Т клетках: понимание патогенеза и терапевтическая цель для аутоиммунных заболеваний.

Ненормальная активация и дифференциация клеток Т имеют решающее значение для патогенез аутоиммунных расстройств. Традиционно, активация клеток Т организуется тремя каноническими сигналами: распознаванием антигена через рецептор Т-клеток (TCR) и основным комплексом гистокомпьютерной совместимости (MHC), сигналами совместного стимулятора и сигнализацией цитокина. Последние исследования показали, что питательные вещества являются ключевым четвертым сигналом модуляции иммунитета клеток Т. Метаболизм клеток Т является неотъемлемой частью регулирования распространения клеток, их выживания и дифферен

Совпадение в аннотации оригинала
Abnormal T-cell activation and differentiation are pivotal in the pathogenesis of autoimmune disorders. Traditionally, T cell activation is orchestrated by three canonical signals: antigen recognition through the T-cell receptor (TCR) and major histocompatibility complex (MHC) interaction, co-stimulatory signals, and cytokine signaling. Recent studies have h…

Shedding Light on the Role of ERAP1 in Axial Spondyloarthritis.

Spondyloarthritis (SpA) is a multifactorial chronic inflammatory disease affecting the axial skeleton (axSpA) and/or peripheral joints (p-SpA) and entheses. The disease's pathogenesis depends on genetic, immunological, mechanical, and environmental factors. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme that shapes the peptide repertoire presented by major histocompatibility complex (MHC) class I molecules. Genome-wide association studies (GWAS) have identified different single nucleotide polymorphisms (SNPs) in ERAP1 that are associated with several autoimmune dise…

Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis.

The intestinal epithelium plays critical roles in sensing and integrating dietary and microbial signals. How microbiota and intestinal epithelial cell (IEC) interactions regulate host physiology in the proximal small intestine, particularly the duodenum, is unclear. Using single-cell RNA sequencing of duodenal IECs under germ-free (GF) and different conventional microbiota compositions, we show that specific microbiota members alter epithelial homeostasis by increasing epithelial turnover rate, crypt proliferation, and major histocompatibility complex class II (MHCII) expression. Microbiome pr…

Role of immunoproteasomes and thymoproteasomes in health and disease.

The proteasome is a multisubunit protease that degrades intracellular proteins into small peptides. Besides playing a pivotal role in many cellular processes indispensable for survival, it is involved in the production of peptides presented by major histocompatibility complex class I molecules. In addition to the standard proteasome shared in all eukaryotes, jawed vertebrates have two specialized forms of proteasome known as immunoproteasomes and thymoproteasomes. The immunoproteasome, which contains cytokine-inducible catalytic subunits with distinct cleavage specificities, produces peptides …

Muscle inflammatory pattern in alpha- and gamma-sarcoglycanopathies.

AIM: Since the immune system plays a role in the pathogenesis of several muscular dystrophies, we aim to characterize several muscular inflammatory features in α- (LGMD R3) and γ-sarcoglycanopathies (LGMD R5). MATERIALS AND METHODS: We explored the expression of major histocompatibility complex class I molecules (MHCI), and we analyzed the composition of the immune infiltrates in muscle biopsies from 10 patients with LGMD R3 and 8 patients with LGMD R5, comparing the results to Duchenne muscular dystrophy patients (DMD). RESULTS: A consistent involvement of the immune response was observed i…

Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases.

DO (HLA-DO, in human; murine H2-O) is a highly conserved nonclassical major histocompatibility complex class II (MHC II) accessory molecule mainly expressed in the thymic medulla and B cells. Previous reports have suggested possible links between DO and autoimmunity, Hepatitis C (HCV) infection, and cancer, but the mechanism of how DO contributes to these diseases remains unclear. Here, using a combination of various in vivo approaches, including peptide elution, mixed lymphocyte reaction, T-cell receptor (TCR) deep sequencing, tetramer-guided naïve CD4 T-cell precursor enumeration, and whole-…