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The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation.

Superantigens (SAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (MHC) class II, conventionally through the variable β-domain of TCR (TCRVβ). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (SEH) and its human receptors, MHC class II and TCR. The structure demonstrates that SEH predominantly interacts with the variable α-domain of TCR (TCRVα), which…

[Genetic factors in multiple sclerosis and neuromyelitis optica].

The pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) results from complex interactions between multiple genetic and environmental factors, both of which can confer susceptibility or resistance to the diseases. To date, genome-wide association studies of European descendants have identified 110 variants associated with MS that are outside of the major histocompatibility complex region. It is noteworthy that most of these variants involve immunologically relevant genes. Nevertheless, the majority of heritability of MS and NMO remain to be discovered (missing heritability). …

Antigen-presenting cells in the skin and placenta in pemphigoid gestationis.

In pemphigoid gestationis (PG), one of the major initiating events is the aberrant expression of the class II molecules of the major histocompatibility complex in the placenta. We used a panel of 13 monoclonal antibodies to investigate the phenotype of the MHC class II positive antigen-presenting cells (APC) in the skin and placenta in PG. In the skin, the APC show reactivity with a variety of macrophage markers and the CDI marker of Langerhans cells. By contrast, the MHC class II positive cells in the placenta showed no reactivity with macrophage or Langerhans cell markers, but were the cytok…

T cells targeted against a single minor histocompatibility antigen can cure solid tumors.

T cells responsive to minor histocompatibility (H) antigens are extremely effective in curing leukemia but it remains unknown whether they can eradicate solid tumors. We report that injection of CD8(+) T cells primed against the immunodominant H7(a) minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)-gamma-producing H7(a)-specific T cells. Intratumoral release of IFN-gamma had two crucial effects: inhibition of tumor angiogenesis and upregulation of major histocompatibility complex (MHC) class…

PCR-SSO typing in HLA-disease association studies.

Associations between a large number of diseases and markers within the major histocompatibility complex (MHC) have been described. In particular, susceptibility to several autoimmune disorders, including type I diabetes mellitus and rheumatoid arthritis, is linked to genes within the MHC and strong population associations are demonstrable between certain HLA class II alleles and these conditions. Genetic mapping of HLA susceptibility loci has traditionally relied on the use of phenotypic markers defined by alloantisera, cellular typing reagents and biochemical analysis of histocompatibility an…

Kawasaki disease: update on diagnosis, treatment, and a still controversial etiology.

Diagnosis of Kawasaki syndrome still relies solely on clinical criteria because the etiology is unknown. However, the function and structure of different bacterial superantigens as potential pathogens are discussed. In this regard, the recent determination of the crystal structure of the toxic shock syndrome toxin-1 superantigen complexed with major histocompatibility complex class II suggests potential implications for the controversial findings concerning a role of those superantigens in Kawasaki disease. Although a specific therapy is not available, coronary complications can be significant…

Parental HLA compatibility, fetal wastage and neural tube defects: evidence for a T/t-like locus in humans.

To test the hypothesis that a locus in or near the human major histocompatibility complex (HLA) contributes to both involuntary fetal loss and neural tube defects (NTD), we evaluated sharing of antigens of the HLA-A, HLA-B, or HLA-DR loci of couples who had three or more first-trimester spontaneous abortions or who had a child with an NTD (myelomeningocele or anencephaly). HLA-A antigen sharing was increased in couples with three or more spontaneous abortions and in couples who had an anencephalic fetus, when compared with couples who had three or more pregnancies and no fetal loss. Increased …

[Pemphigoid gestationis after egg donation : A case report].

Pemphigoid gestationis (PG) is a blistering autoimmune skin disease, typically occurring in the second and third trimester of pregnancy. Aberrant expression of major histocompatibility complex (MHC) class II molecules on the chorionic villi seems to lead to antibody production against bullous pemphigoid (BP)-180. We report a case of PG in a woman whose pregnancy was achieved using egg donation. Since the entire fetal genome is allogeneic to the mother, augmented immune reaction in egg-donated pregnancies appears to trigger the occurrence of PG.

Вирусы, преподающие иммунологию: роль модели ЛСМВ и человеческих вирусных инфекций в иммунологических открытиях.

Вирология сыграла важную роль в расшифровке многих иммунологических явлений, тем самым формируя наше нынешнее понимание иммунной системы. Зверские модели вирусной инфекции и вирусных инфекций человека являются важными инструментами для иммунологических открытий. В настоящем обзоре рассматриваются два иммунологических прорыва, которые первоначально были выявлены с помощью модели лимфоцитного хориоменингита (ЛКМВ); иммунологические ограничения, обусловленные основными гистокомпьютерными комплексами, и иммунная терапия с помощью блокировки контрольно-пропускных пунктов. Кроме того, мы обсуждаем т

Совпадение в аннотации оригинала
Virology has played an essential role in deciphering many immunological phenomena, thus shaping our current understanding of the immune syst … with the help of the lymphocytic choriomeningitis virus (LCMV) model; immunological restriction by major histocompatibility complex and immunotherapy using checkpoint blockade. In addition, we discuss related discoveries such as development of tetramers, viral escape mutation, and the phenomenon of T-cell exhaustion.

Anti-class II MHC antibodies prevent and treat EAE without APC depletion.

We have demonstrated that a murine IgG1 anti-class II major histocompatibility complex (MHC) antibody (OX6) is able both to prevent and treat experimental autoimmune encephalomyelitis (EAE) in the Biozzi AB/H mouse. We have confirmed that this antibody is poorly cytotoxic, allowing mechanisms of action other than depletion of antigen-presenting cells (APC) to be assessed. Despite its effect on disease, OX6 administration does not prevent priming of T cells in the draining lymph node, implying an alternative mechanism for regulation of the autoimmune disease process.

The prevalence, molecular analysis and HLA typing of late-onset 21-hydroxylase deficiency in Turkish woman with hirsutism and polycystic ovary.

We studied the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 2l-hydroxylase (21-OH) deficiency, its molecular genotype expression, and its association with the major histocompatibility complex in 61 women with hirsutism and polycystic ovary. Ultrasound, clinical and hormonal parameters were used to define polycystic ovary syndrome (PCOS). Baseline and ACTH stimulated 17alpha-hydroxyprogesterone (17-OHP) levels were measured for screening of LOCAH during follicular phase. Forty-one women were diagnosed as having PCOS (67%) and 20 women were diagnosed as having had LOCAH …

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32.

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

Susceptibility to murine lymphocytic choriomeningitis maps to class I MHC genes--a model for MHC/disease associations.

Susceptibility to some human diseases is linked, albeit weakly, to major transplantation antigens (HLA) encoded by the major histocompatibility gene complex (MHC). Here we have studied MHC/disease association in inbred strains of mice after intracerebral (i.c.) injection of lymphocytic choriomeningitis virus (LCMV). This route of infection leads to a lymphocytic choriomeningitis (LCM) which is not the result of direct cytopathic effects of the virus but is caused by the induced T-cell immune response: immunocompetent mice die whereas T-cell-deficient mice survive. By using two plaque variants

Haplotype associations of the MHC with psoriasis vulgaris in Chinese Hans.

Summary Haplotype associations of the major histocompatibility complex (MHC) with psoriasis vulgaris (PV) have been demonstrated in different racial or ethnic populations. The objective of this study was to demonstrate the different haplotype associations of the MHC in Chinese patients with psoriasis according to the type of onset and their sex. One hundred and thirty-eight patients with PV and 149 normal control subjects without psoriasis were typed for HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 by using the PCR with sequence-specific primers. The results showed: (i) HLA-A*26 (26.1% vs. 12.1%, Pc …

Expression of MHC class II molecules on human monocytes is regulated independently from each other after phagocytosis of bacteria.

Reactive arthritis is usually self-limiting polyarthritis which develops in HLA-B27 positive individuals after certain gastrointestinal or urogenital infections. The pathogenesis of reactive arthritis is unknown but T cells seem to have a crucial role. Most of the antigen-specific T cells isolated from the synovial fluid have been MHC class II restricted. The role of antigen presentation in the pathogenesis of reactive arthritis has been studied relatively little. In this work the authors studied the effect of arthritis-triggering bacterium (Yersinia enterocolitica O:3) on the expression of MH

Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome.

Bare lymphocyte syndrome (BLS) is an autosomal recessive severe-combined immunodeficiency that can result from mutations in four different transcription factors that regulate the expression of major histocompatibility complex (MHC) class II genes. We have identified here the defective gene that is responsible for the phenotype of the putative fifth BLS complementation group. The mutation was found in the regulatory factor that binds X-box 5 (RFX5) and was mapped to one of the arginines in a DNA-binding surface of this protein. Its wild-type counterpart restored binding of the RFX complex to DN…

Autoreactive CD8-specific T-cell response in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Autoimmune attack in PBC is predominantly organ-specific, despite the presence of mitochondrial autoantigens, the major targets of autoimmunity in PBC, in all nucleated cells. Cytotoxic T lymphocytes are thought to be directly involved in the tissue injury in PBC. The major histocompatibility complex (MHC) class I-restricted epitope for E2 components of pyruvate dehydrogenase complexes, namely amino acid 159-167, a region very close to the epitoperecognized by MHC class II-restricted CD4 cells and by antibody, …

Antigen presentation: lysoyme, autoimmune diabetes, and Listeria--what do they have in common?

We discuss three areas of antigen presentation and macrophage biology being investigated in the laboratory. Using hen egg-white lysozyme as a protein antigen, all the segments of the molecules selected by the class II histocompatibility molecule I-A(k) were identified and characterized. The display of each family of peptides was explained biochemically and quantitated. Conformational isomers of a peptide-major histocompatibility complex (MHC) complex were identified. The relationship between the amounts of peptide-MHC displayed by the antigen-presenting cells and two biologic responses, centra…

STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-I-Transformed and ATL Cells.

We have previously reported on the deregulation of cellular microRNAs involved in hematopoiesis and inflammation in human T-cell lymphotropi … her demonstrate that increased expression of STAT1 in ATL cells is associated with higher levels of major histocompatibility complex class I expression. Previous studies have demonstrated that the pressure exerted by natural killer (NK) cells in vivo can edit leukemic tumor cells by forcing an increased expression of major histocompatibility complex class I to escape immune clear …