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Characterization of Human Type C Enterotoxin Produced by Clinical S. epidermidis Isolates.

Staphylococcal Enterotoxins (SEs) are superantigens (SAg) originally produced by S. aureus, but their presence in coagulase negative staphylococci (CNS) has long been suspected. This study aims to better characterize a novel C-like enterotoxin expressed by clinical S. epidermidis strains, called SECepi. We isolated and characterized SECepi for its molecular and functional properties. The toxin was structurally modeled according to its significant similarity with S. aureus SEC3. Most of SEC amino acid residues important for the formation of the trimolecular Major Histocompatibility Complex II M…

M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8+ T Cells with Reduced Proliferative Capacity.

CD8+ cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ activation status influences their antigen presentation function to CD8+ T cell in models of…

A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-b … S1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal pep …

Detection of antigen-specific T cells on p/MHC microarrays.

The development of high-throughput protein microarrays for rapidly determining antigen-specific T-cell receptor repertoires of diverse T-cell populations can enable comprehensive, broad-based analyses of T-cell responses. Promising applications include medical diagnostics, vaccine development, treatment of autoimmune diseases and detection of potential agents of bioterrorism. In this study, we examined the feasibility of using peptide/major histocompatibility complex (p/MHC) microarrays to selectively capture and enumerate antigen-specific T cells. Results are presented for p/MHC microarrays c…

Familial collapsing glomerulopathy: clinical, pathological and immunogenetic features.

BACKGROUND: Collapsing glomerulopathy (CG) is an aggressive form of glomerular injury frequently seen in association with HIV infection, although it is also recognized in non-HIV patients as a primary disease. Until now, the occurrence of CG in a familial pattern has not been reported. METHODS: We studied five members of a family (siblings), admitted for evaluation of proteinuria and nephrotic syndrome. They had no other family history of renal disease. Blood samples for major histocompatibility complex (MHC) analysis were obtained from the five siblings, both parents and four relatives. RES…

Combination biologic therapy.

Biologic therapies refer to genetically engineered treatments such as monoclonal antibodies and receptor-immunoglobulin fusion proteins. Following many disappointments, the introduction of anti-tumor necrosis factor (anti-TNF alpha) therapies into the clinic has clearly demonstrated the exciting potential of biologic agents. Many of these have been designed to modulate a specific aspect of the underlying autoimmune process, thus avoiding generalized immunosuppression. They include products which interfere with the trimolecular complex of major histocompatibility complex II-Antigen-T cell recep…

Hepatic lesions induced by graft-versus-host reaction across MHC class II antigens: an implication for animal model of primary biliary cirrhosis.

To induce graft-versus-host reaction (GVHR), C57B1/6 (B6) spleen cells were injected into (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice. Since the strains bm1 and bm12 are mutant at the H-2Kb and I-Ab regions of major histocompatibility complex (MHC), respectively, we can assess MHC class I- or class II-different GVHR. As reported earlier, immunological perturbations assessed by the number of immunoglobulin-producing cells and immune complex deposition in renal glomeruli were demonstrated in MHC class II-different GVHR. A conspicuous finding in this report is that epithelioid granuloma …

T-cell receptors of human suppressor cells.

Cells which can suppress the immune response to an antigen (TS cells) appear to be essential for regulation of the immune system. But the ch … epromatous leprosy patients which carry the CD8 antigen and recognize antigen in the context of the major histocompatibility complex (MHC) class II molecules in vitro. We here report the characterization of additional MHC-restricted TS clones which rearrange TCR beta genes, express messenger RNA for the alpha and beta chains of the TCR and express clonally unique CD3-associated T …

Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.

Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent …

Conformational Plasticity of HLA-B27 Molecules Correlates Inversely With Efficiency of Negative T Cell Selection.

The development of autoimmune disorders is incompletely understood. Inefficient thymic T cell selection against self-peptides presented by major histocompatibility antigens (HLA in humans) may contribute to the emergence of auto-reactive effector cells, and molecular mimicry between foreign and self-peptides could promote T cell cross-reactivity. A pair of class I subtypes, HLA-B2705 and HLA-B2709, have previously been intensely studied, because they are distinguished from each other only by a single amino acid exchange at the floor of the peptide-binding groove, yet are differentially associa

Beyond gluten: the multifaceted regulation of MHC class II in celiac disease pathogenesis.

Celiac disease (CD) is a complex immune-mediated disorder influenced by genetic predispositio and environmental triggers, which human leukocyte antigen (HLA)-DQ2/8 playing a central role in disease pathogenesis. Gluten peptides deamidated by tissue transglutaminase 2 (tTG2) bind to CD4⁺ T cells via major histocompatibility complex (MHC) class II molecules, initiating an inflammatory cascade that damages the intestinal mucosa. Although many individuals carry HLA-DQ2/8 alleles, only a subset develops CD, suggesting the contribution of additional regulatory factors. This review examines the criti…

Change in nomenclature for the immunologic synapse from Troxis Necrosis to trogocytosis.

The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the …

Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.

Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genom … sm at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹⁵). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). T …

Polymorphisms in the 2q33 and 3q21 chromosome regions including T-cell coreceptor and ligand genes may influence susceptibility to pemphigus foliaceus.

Signaling through antigen presenting cells is required to activate T lymphocytes. The antigen-specific signal is given by interaction of the T-cell receptor (TCR) with the major histocompatibility complex (MHC)/peptide complex. Also essential for activation is the interaction of the coreceptor CD28 with ligands of the B7 family (CD80 and CD86) on antigen presenting cells. Coreceptor CTLA-4 is a negative regulator and binds the same B7 isoforms, contributing to immunologic homeostasis and peripheral tolerance. CD28 and CTLA4 are homologous and closely linked genes in 2q33, as are CD80 and CD86 …

Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells.

The thymus develops from the third pharyngeal pouch of the anterior gut and provides the necessary environment for thymopoiesis (the process … y cultured while conserving the capacity to integrate in a thymic epithelial network and to express major histocompatibility complex class II (MHC II) molecules and Aire. These cells can irreversibly adopt the fate of hair follicle multipotent stem cells when exposed to an inductive skin microenvironment; this change in fate is correlated with robust changes in gene expression. H …

Structure and function of the bovine fetomaternal unit in relation to the causes of retained fetal membranes.

Approximately 5 per cent of dairy cows are affected by retained fetal membranes. Retained fetal membranes are an important risk factor for t … a and its separation from healthy caruncles depends upon incompatibility between maternal and fetal major histocompatibility complex class I expressed on epithelium within the fetomaternal unit. Placental maturation follows stimulation of the maternal immune response and the production of neutrophil-activating factors within the epithelium in the caruncular arcade. This affects t …

Реакция CD8+T-клеток на лимфоцитный хориомингит включает в себя антиген L: обнаружение новых трюков для старого вируса.

CD8(+) Реакции T-клеток контролируют лимфоцитный хориомингит (LCMV) инфекцию H-2(b) мышей. Хотя антигенные реакции на инфекцию ЛКМВ хорошо изучены, мы обнаружили, что значительная часть реакции CD8(+) CD44(hi) T-клеток на ЛСМВ в H-2(b) мышах не была учтена известными эпитопами. Мы проверили пептиды, которые, по прогнозам, будут связывать основной гистокомпьютерный сложный класс I и перекрывать 15-мерные пептиды, охватывающие полный протеом ЛКМВ для гамма-интерферона (IFN-гамма) инъекции из CD8(+) Т клеток, полученных из мышей, инфицированных ЛCMV-H-2(b). Мы определили 19 новых эпитопов. Вместе

Совпадение в аннотации оригинала
CD8(+) T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2(b) mice. Although antigen-specific responses agai … LCMV in H-2(b) mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-gamma) induction from CD8(+) T cells derived from LCMV-infected H-2(b) mice. We identified 19 novel epitopes. Together with the 9 previously known, …

HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset.

Generalized vitiligo is a common autoimmune disorder characterized by white patches of skin and overlying hair caused by loss of pigment-for … enetic component, and perhaps stronger associations with specific alleles. To determine whether the major histocompatibility complex (MHC) contributes to the familial clustering of vitiligo and vitiligo-associated autoimmune/autoinflammatory diseases, we performed case-control and family-based association analyses of HLA class II-DRB1 and -DQB1 alleles and haplotypes in affected …

Staphylococcal enterotoxin microbial superantigens.

Staphylococcal enterotoxins are a family of structurally related proteins that are produced by Staphylococcus aureus. In addition to their r … T lymphocytes known. The receptors for staphylococcal enterotoxins on antigen-presenting cells are major histocompatibility complex (MHC) class II molecules. Further, the alpha-helical regions of the class II molecule are essential for function and appear to interact directly with the NH2-terminal region of staphylococcal enterotoxins such as SEA. Recent studies have shown that …

PIK3C3/VPS34 helps school T cells in the thymus.

The development of a broad repertoire of T cells in the immune system requires interaction of T cell receptors expressed by immature T cells with peptide/major histocompatibility complexes (MHCs) displayed by specialized epithelial cells in the thymus, in a process called T cell positive selection. Thymic epithelial cells (TECs) display unique antigen processing machinery which shapes the collection of self-peptides that drive positive selection. In our recent studies, we explored the contribution of the lipid kinase PIK3C3/VPS34 to the generation of positively selecting peptides in TECs. We f…