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CD4+ T Cells: guardians of the phagosome.

CD4(+) T cells are key cells of the adaptive immune system that use T cell antigen receptors to recognize peptides that are generated in endosomes or phagosomes and displayed on the host cell surface bound to major histocompatibility complex molecules. These T cells participate in immune responses that protect hosts from microbes such as Mycobacterium tuberculosis, Cryptococcus neoformans, Leishmania major, and Salmonella enterica, which have evolved to live in the phagosomes of macrophages and dendritic cells. Here, we review studies indicating that CD4(+) T cells control phagosomal infection…

Comprehensive association analysis of candidate genes for generalized vitiligo supports XBP1, FOXP3, and TSLP.

We previously carried out a genome-wide association study of generalized vitiligo (GV) in non-Hispanic whites, identifying 13 confirmed susc … be secondary to epidemiological association with other concomitant autoimmune diseases. Within the major histocompatibility complex (MHC), at 6p21.33, association with TAP1-PSMB8 (rs3819721, P=5.2E-06) seems to derive from linkage disequilibrium with major primary signals in the MHC class I and class II regions.

Phagocytosis of Fonsecaea pedrosoi conidia, but not sclerotic cells caused by Langerhans cells, inhibits CD40 and B7-2 expression.

Fonsecaea pedrosoi is the major etiological agent of chromoblastomycosis, a chronic, suppurative, granulomatous mycosis usually confined to skin and subcutaneous tissues, presenting a worldwide distribution. The host defense mechanisms in chromoblastomycosis have not been extensively investigated. Langerhans cells (LC) are bone-marrow-derived, dendritic antigen-presenting cells of the epidermis, which constitutively express major histocompatibility complex (MHC) class II, and comprise 1-3% of total epidermal cells. LC are localized in suprabasal layers of the epidermis and in mucosa, where the…

HLA-A2-restricted human CD8(+) cytotoxic T lymphocyte responses to a novel epitope in vaccinia virus that is conserved among orthopox viruses.

Classical major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in protective immunity against infection with smallpox virus. The identification of target antigens is crucial for defining the role played by CD8(+) CTL responses in host resistance to smallpox and for the design of vaccines that produce effective cell-based responses. We report the identification of a novel human leukocyte antigen-A*0201-restricted epitope (J8R(11-19)) within A55R of vaccinia virus (VV) that is conserved in J8R of smallpox virus variola major. The J8R(11…

The Role of PPARgamma Ligands as Regulators of the Immune Response.

A major challenge in medical research is to break the traditional compartmentalization that frequently separates different fields. Unexpecte … he antidiabetic thiazolidinediones group exert beneficial effects on atherosclerosis. Expression of major histocompatibility complex class II (MHC class II), a key molecule in the immune response, has recently been observed in atherosclerotic plaques. In recent years, important effects of PPARgamma ligands on MHC class II expression, activated T lymphocytes and macrophage activat …

High-level expression of viral interleukin-10 in cardiac allografts fails to prolong graft survival.

BACKGROUND: Viral interleukin (vIL)-10, encoded in the Epstein-Barr virus genome, shares many of the anti-inflammatory properties of cellular IL-10 but is supposed to lack IL-10's immunostimulatory properties. Thus, vIL-10 is expected to offer superior immunosuppression. METHODS: We established transgenic mice (vIL-10 Tg) that express vIL-10 systemically and transplanted their hearts as vascularized allografts into unmodified major histocompatibility complex (MHC) full-mismatch or MHC class II-disparate mice. RESULTS: The vIL-10 Tg mice revealed high-level expression of vIL-10 in major organ…

Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis.

Polymyositis (PM) is an autoimmune inflammatory muscle disease of unknown cause in which cellular immunity is thought to play an important pathogenic role. Class II major histocompatibility complex (class II MHC: human leukocyte antigen (HLA)-DR operates as a cofactor of antigen presentation in immunological responses. There has been a major debate over whether muscle fibers themselves synthesize and express HLA-DR molecules and play a role in antigen presentation in PM pathogenesis. In this study, we demonstrated that most muscle fibers from patients with PM synthesized and expressed HLA-DR m…

Deletion of self-reactive thymocytes occurs at a CD4+8+ precursor stage.

As T cells develop in the thymus, they become tolerant of self-antigens. A major advance in the understanding of how this process occurs was … icipants in the self-recognition process that leads to clonal elimination, and that thymic class II major histocompatibility complex (MHC) molecules can influence the repertoire of CD4-8+ cells.

Targeting HIV-1 immune escape mechanisms: Key advances and challenges in HIV-1 vaccine design.

Despite numerous efforts, a successful vaccine against HIV-1 remains elusive. An effective vaccine must overcome the virus's sophisticated immune evasion strategies and induce the production of broadly neutralizing antibodies to counteract HIV-1's rapid mutation, replication, and transmission within and between hosts. HIV-1 predominantly evades immune recognition and clearance through mechanisms such as genomic mutations, alterations in envelope protein affinity, the formation of latent viral reservoirs, and interference with major histocompatibility complex class I antigen presentation. Altho…

Impact of VHSV on CIITA-mediated MHCII expression and antigen presentation in largemouth bass.

Viral hemorrhagic septicemia virus (VHSV) infection poses a significant threat to fish immunity by evading antigen presentation. Our previous study indicated that VHSV inhibited the transcriptional activation of MHC class II (MHCII) to impair antigen presentation in vitro, but the underlying mechanisms remain unclear. Here, we cloned and characterized the class II major histocompatibility complex transactivator (CIITA) in largemouth bass (Micropterus salmoides), a key regulator of MHCII expression, demonstrating that it activates MHCII transcription and possesses antiviral properties against V…

GWAS подчеркивает невральный вклад в подверженность множественным склерозам.

Множественный склероз (MS) — хроническое воспалительное и нейродегенеративное заболевание мозга и спинного мозга. Генетические исследования выявили множество рисковых лоси, которые, как считалось, в первую очередь влияют на иммунные клетки и микроглию. Здесь мы провели многокантрольное исследование генома связи с 20,831 МЗ и 729,220 контроль за участниками, выявление 236 Возможные варианты уязвимости за пределами основного комплекса four Роман-лочи. Мы вычислили полигенный балл для MS и, оптимизированный для европейского происхождения, он является информативным для афро-американских и латиноам

Совпадение в аннотации оригинала
Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have id … ith 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci. We derived a polygenic score for MS and, optimized for European ancestry, it is informative for African-American and Latino participants. Integrating single-cell data from blood and brain tissue, we identified 76 genes af …

SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions.

A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the type I interferon (IFN-I) response and to downregulate major histocompatibility complex I (MHC-I) cell surface levels, but had no …

T cells in the pathogenesis of axial spondyloarthritis.

Axial spondyloarthritis (axSpA) is the prototype of the spondyloarthritis spectrum. The involvement of T cells in its pathogenesis has long been suspected on the basis of the association with the major histocompatibility complex I molecule HLA-B27 and the pivotal role of interleukin 17 in the inflammatory mechanisms associated with the disease. Moreover, the presence of unconventional or "innate-like" T cells within the axial enthesis suggests an important role for these cells in the pathophysiology of the disease. In this review, we describe the characteristics and the interleukin 17 secretio…

Possible roles of HLA-G regulating immune cells in pregnancy and endometrial diseases via KIR2DL4.

Major histocompatibility complex (MHC) molecules bind peptides originated from cellular synthesis and present them at the cell surface for recognition by receptors on immune cells like T lymphocytes, natural killer (NK) cells or mast cells. Such recognition plays a crucial part in autoimmunity, anti-bacterial, anti-viral and anti-tumor responses. Human leukocyte antigen G (HLA-G) is a member of non-classical HLA class I molecules which has been studied deeply in recent years into its role in pregnancy and endometrial diseases, including endometrial tumor, endometriosis and adenomyosis, etc. Un…

MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses.

Recent outbreaks of Ebola virus (EBOV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have exposed our limited therapeutic options for such diseases and our poor understanding of the cellular mechanisms that block viral infections. Using a transposon-mediated gene-activation screen in human cells, we identify that the major histocompatibility complex (MHC) class II transactivator (CIITA) has antiviral activity against EBOV. CIITA induces resistance by activating expression of the p41 isoform of invariant chain CD74, which inhibits viral entry by blocking cathepsin-mediated pr…

WDFY4 is required for cross-presentation in response to viral and tumor antigens.

During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain-containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3 -/- mice, Wdfy4 -/…

Autophagy Proteins in Phagocyte Endocytosis and Exocytosis.

Autophagy was initially described as a catabolic pathway that recycles nutrients of cytoplasmic constituents after lysosomal degradation during starvation. Since the immune system monitors products of lysosomal degradation via major histocompatibility complex (MHC) class II restricted antigen presentation, autophagy was found to process intracellular antigens for display on MHC class II molecules. In recent years, however, it has become apparent that the molecular machinery of autophagy serves phagocytes in many more membrane trafficking pathways, thereby regulating immunity to infectious dise…

Genetic associations and functional characterization of M1 aminopeptidases and immune-mediated diseases.

Endosplasmic reticulum aminopeptidase 1 (ERAP1), endoplasmic reticulum aminopeptidase 2 (ERAP2) and puromycin-sensitive aminopeptidase (NPEPPS) are key zinc metallopeptidases that belong to the oxytocinase subfamily of M1 aminopeptidase family. NPEPPS catalyzes the processing of proteosome-derived peptide repertoire followed by trimming of antigenic peptides by ERAP1 and ERAP2 for presentation on major histocompatibility complex (MHC) Class I molecules. A series of genome-wide association studies have demonstrated associations of these aminopeptidases with a range of immune-mediated diseases s…

Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality?

T cells reactive to lipids and restricted by major histocompatibility complex (MHC) class I-like molecules represent more than 15% of all lymphocytes in human blood. This heterogeneous population of innate cells includes the invariant natural killer T cells (iNK T), type II NK T cells, CD1a,b,c-restricted T cells and mucosal-associated invariant T (MAIT) cells. These populations are implicated in cancer, infection and autoimmunity. In this review, we focus on the role of these cells in autoimmunity. We summarize data obtained in humans and preclinical models of autoimmune diseases such as prim…

Необузданность против восстановления после острого вируса гепатита С из общего источника.

Острая инфекция гепатитом С (ГХВ) редко выявляется, и поэтому факторы, определяющие спонтанное разрешение и хроническость, по-прежнему не до конца понимаются. В частности, из-за ретроспективного характера и неизвестного источника инфекции в большинстве исследований человека прямые свидетельства появления мутаций от бегства в иммунодоминантных сложных гистокомплексных эпитопах класса I, ограничивающихся иммунитетом, крайне ограничены. В двух пациентах, которые случайно заразились идентичным штаммом HCV, но у которых появились различные результаты, полное отсутствие клеток HCV CD4+T в сочетании

Совпадение в аннотации оригинала
Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity r … nfection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I-restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigo …