Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with CELIAC DISEASE.Glutens: Prolamins in the endosperm of SEEDS from the Triticeae tribe which includes species of WHEAT; BARLEY; and RYE.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Celiac Disease: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.Diet, Gluten-Free: A diet which is devoid of GLUTENS from WHEAT; BARLEY; RYE; and other wheat-related varieties. The diet is designed to reduce exposure to those proteins in gluten that trigger INFLAMMATION of the small intestinal mucosa in patients with CELIAC DISEASE.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Triticum: A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS.Transglutaminases: Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Immunity, Humoral: Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.Cell Migration Inhibition: Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis.Flour: Ground up seed of WHEAT.Prolamins: A group of seed storage proteins restricted to the POACEAE family. They are rich in GLUTAMINE and PROLINE.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Jejunum: The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Immunity, Mucosal: Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.Adaptive Immunity: Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).Mice, Inbred BALB CLymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Mice, Inbred C57BLImmunity, Maternally-Acquired: Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Duodenum: The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers.Vaccines, DNA: Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Spleen: An encapsulated lymphatic organ through which venous blood filters.Leukocyte Migration-Inhibitory Factors: Protein factor(s) released by sensitized lymphocytes (and possibly other cells) that inhibit the movement of LEUKOCYTES, especially polymorphonuclear cells, away from their site of release. Assays for these factors are used as tests for cellular immunity. Two of the common assays are the LEUKOCYTE MIGRATION CAPILLARY TUBE TECHNIQUE (LMCT) and the LEUKOCYTE MIGRATION AGAROSE TEST (LMAT).Lactoglobulins: Globulins of milk obtained from the WHEY.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Reticulin: A scleroprotein fibril consisting mostly of type III collagen. Reticulin fibrils are extremely thin, with a diameter of between 0.5 and 2 um. They are involved in maintaining the structural integrity in a variety of organs.Wheat Hypersensitivity: Allergic reaction to wheat that is triggered by the immune system.Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Avena sativa: A plant species of the family POACEAE that is widely cultivated for its edible seeds.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens in food.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Epitopes: Sites on an antigen that interact with specific antibodies.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Plant Immunity: The inherent or induced capacity of plants to withstand or ward off biological attack by pathogens.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.Pancreatin: A mammalian pancreatic extract composed of enzymes with protease, amylase and lipase activities. It is used as a digestant in pancreatic malfunction.Secale cereale: A hardy grain crop, rye, grown in northern climates. It is the most frequent host to ergot (CLAVICEPS), the toxic fungus. Its hybrid with TRITICUM is TRITICALE, another grain.Antigens, Plant: Substances found in PLANTS that have antigenic activity.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Vaccines, Synthetic: Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.Zea mays: A plant species of the family POACEAE. It is a tall grass grown for its EDIBLE GRAIN, corn, used as food and animal FODDER.Hemadsorption Inhibition Tests: Serological tests that measure anti-hemadsorption agents such as antiviral ANTIBODIES that block VIRAL HEMAGGLUNININS from adhering to the surface of red blood cells.Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients.Enterocytes: Absorptive cells in the lining of the INTESTINAL MUCOSA. They are differentiated EPITHELIAL CELLS with apical MICROVILLI facing the intestinal lumen. Enterocytes are more abundant in the SMALL INTESTINE than in the LARGE INTESTINE. Their microvilli greatly increase the luminal surface area of the cell by 14- to 40 fold.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Immunization, Secondary: Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.AIDS Vaccines: Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Intradermal Tests: Skin tests in which the sensitizer is injected.Hemocytes: Any blood or formed element especially in invertebrates.Listeriosis: Infections with bacteria of the genus LISTERIA.Animal Feed: Foodstuff used especially for domestic and laboratory animals, or livestock.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Bread: Baked food product made of flour or meal that is moistened, kneaded, and sometimes fermented. A major food since prehistoric times, it has been made in various forms using a variety of ingredients and methods.Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.DisaccharidasesListeria monocytogenes: A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion.Cytotoxicity Tests, Immunologic: The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Cereals: Seeds from grasses (POACEAE) which are important in the diet.Dinitrochlorobenzene: A skin irritant that may cause dermatitis of both primary and allergic types. Contact sensitization with DNCB has been used as a measure of cellular immunity. DNCB is also used as a reagent for the detection and determination of pyridine compounds.Enzyme Therapy: The use of enzymes to correct metabolic and physiological processes.Plague Vaccine: A suspension of killed Yersinia pestis used for immunizing people in enzootic plague areas.Dietary Proteins: Proteins obtained from foods. They are the main source of the ESSENTIAL AMINO ACIDS.Caseins: A mixture of related phosphoproteins occurring in milk and cheese. The group is characterized as one of the most nutritive milk proteins, containing all of the common amino acids and rich in the essential ones.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.Interleukin-12: A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.Vaccines, Attenuated: Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity.
  • the lower risk from DQ2.2 relates to constraints imposed on gluten peptides to stably bind this HLA molecule. (nih.gov)
  • Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. (diva-portal.org)
  • Tissue transglutaminase 2 (tTG2) is an intestinal digestive enzyme which deamidates already partially digested dietary gluten e.g. gliadin peptides. (jove.com)
  • In this instance, it was shown in transgenic HLA-DQ8 mice, and for some human CD4 T-cell clones, that gliadin peptides were recognized by T-cell receptors (TCRs) bearing a negatively charged residue in the first segment of the CDR3β loop ( 12 ). (diabetesjournals.org)
  • Gliadin peptides are able to activate both intraepithelial lymphocytes (IELs), in particular CD8+ TCRαβ+ lymphocyte bearing the CD94 receptor (NKT cells), and lamina propria CD8+TCRαβ+ lymphocytes of the adaptive immunity. (els.net)
  • Several gluten peptides (as p123-132) are able to bind to HLA‐class I molecules (in particular to HLA‐A1, A2 and B8) expressed on the surface of both dendritic cells and epithelial cells, and are specifically recognised by CD8+TCRαβ+ in the lamina propria. (els.net)
  • On the other hand, peptides such as 31-43 or 31-55 of α‐gliadin stimulate enterocyte to produce IL15 that, in turn, induces the autocrine overexpression of stress molecules MICA and MICB. (els.net)
  • 2009) Intestinal T cell responses to gluten peptides are largely heterogeneous: implications for a peptide‐based therapy in celiac disease. (els.net)
  • In this study, we propose a revised model that is based on the ability of the BCR to serve as a substrate to TG2 and become cross-linked to gluten-derived peptides. (jimmunol.org)
  • Key players in the immune reaction leading to pathogenic destruction of the intestinal epithelium are CD4 + T cells that react specifically with gluten-derived peptides when bound to the predisposing MHC class II molecules HLA-DQ2 (particularly the DQ2.5 variant) and HLA-DQ8. (jimmunol.org)
  • It has been demonstrated that the T cell response generally does not target gluten peptides in their native form but rather their deamidated counterparts in which certain glutamine residues have been converted to glutamic acid, leading to improved binding to the disease-associated HLA molecules ( 2 , 3 ). (jimmunol.org)
  • Investigating the early events of CD, particularly the interaction between undigested gliadin peptides and intestinal epithelial cells, has unveiled the critical role of protein trafficking in the pathogenesis of the disorder. (abcd-it.org)
  • From a general point of view, it is interesting to note that peptides from gliadin, a very common alimentary protein, can have several metabolic effects owing to their ability to interfere with important cellular functions, including those regulated by the endocytic pathway. (abcd-it.org)
  • However, it still remains to be established why P31-43 and other undigested gliadin peptides have such a peculiar effect on the celiac intestinal mucosa and whether they can also be dangerous for the non-celiac intestinal mucosa. (abcd-it.org)
  • A current working hypothesis, corroborated by preliminary observations, is that undigested gliadin peptides have the same effect in controls and CD patients. (abcd-it.org)
  • Celiac disease is driven by intestinal T cells responsive to proline-rich gluten peptides that often harbor glutamate residues formed by tissue transglutaminase-mediated glutamine conversion. (jimmunol.org)
  • The new data extend the knowledge base for understanding the binding of gluten peptides to DQ2.5. (jimmunol.org)
  • From previous studies, it is clear that celiac lesion-derived, gluten-reactive T cells predominantly recognize peptides that cluster within the proline (Pro)-rich regions of gluten proteins ( 2 ), and these peptides contain glutamate (Glu) residues formed in vivo through tissue transglutaminase (TG2)-mediated deamidation of glutamine (Gln) residues ( 1 ). (jimmunol.org)
  • The negative charges introduced by this deamidation process generally increase the binding affinity of gluten peptides to DQ2.5 ( 3 , 4 ). (jimmunol.org)
  • More than 15 different gluten peptides recognized by celiac lesion T cells have been identified ( 2 , 3 , 5 , 6 , 7 ). (jimmunol.org)
  • All B. fragilis strains also showed gliadin-hydrolyzing activity, and some of them generated immunogenic peptides that preserved or increased inflammatory cytokine production (tumor necrosis factor alpha) and showed increased ability to permeate through Caco-2 cell cultures. (asm.org)
  • Other gliadin peptides activate an innate immune response characterized by increased production of IL-15 by epithelial and antigen-presenting cells, which activate the effector function and cytotoxic activity of intraepithelial lymphocytes ( 15 ). (asm.org)
  • Gliadin peptides also induce upregulation of the zonulin innate immunity pathway, which leads to increased intestinal permeability and enables paracellular translocation of gliadin and its subsequent interaction with antigen-presenting cells within the intestinal submucosa ( 11 ). (asm.org)
  • Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for Celiac Sprue," Journal of Proteome Research , vol. 4, no. 5, pp. 1732-1741, 2005. (hindawi.com)
  • Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease," Journal of Experimental Medicine , vol. 205, no. 1, pp. 143-154, 2008. (hindawi.com)
  • This suggests that CD4+ gluten reactive T cells, which are found in CD patients and which recognise gluten peptides deamidated by TG2 in context of DQ2 or DQ8, are implicated in the generation of these autoantibodies. (europa.eu)
  • The onset of type I diabetes at an early age in patients with CD, compared to non-CD, and the prevention or delay in onset of diabetes by gluten-free diet in genetically predisposed individuals substantiates this antigen trigger hypothesis. (asm.org)
  • CTLA-4 is a T-cell co-inhibitory molecule that outcompetes the co-stimulatory molecule CD28 for binding to B7 on antigen-presenting cells, thereby down-modulating cytotoxic T-cell function and allowing cellular proliferation. (biomedcentral.com)
  • In addition to the gliadin fraction of wheat gluten, similar alcohol soluble fractions of barley and rye (hordein and secalin, respectively) are thought to activate the disease process. (bmj.com)
  • We investigated the response to gluten in patients with HLA-DQ2.2. (nih.gov)
  • The CD-associated bacteria also influenced the magnitude of the IL-17A response to gluten. (diva-portal.org)
  • Under these guidelines, any abnormal antibody response to gluten would be considered an allergy. (townsendletter.com)
  • Lamina propria CD4+ T cells are phenotypically activated and produce large amounts of T helper cell type 1 (Th1) cytokines in response to gluten stimulation. (bmj.com)
  • Gluten-free diet-dependent remission of dermatitis in EM96 together with presence of tTG2+IgA+ cells in its skin suggest an autoimmune, DH-like mechanism for the development of this condition. (jove.com)
  • One hypothesis is that IL-15 induces the highly inflammatory Th1 response that activates T-helper cells (DQ2 restricted gliadin specific) that then orchestrate the destructive response, but the reason why inflammatory cells develop prior to gliadin specific helper cells is not known. (wikipedia.org)
  • FODMAPs are present in gluten-containing grains and have recently been identified as a possible cause of gastrointestinal symptoms in NCGS patients, but do not justify extra-digestive symptoms. (wikipedia.org)
  • As a result, NCGS patients often suffer needlessly with symptoms that most probably could be resolved within months with a gluten free diet. (dcorthoacademy.org)
  • NCGS is an emerging condition associated with gluten ingestion and the diagnosis of which is based on exclusion of CD and WA. (symbiosisonlinepublishing.com)
  • Patients with DQ2.2 and no other risk alleles had gluten-reactive T cells that did not respond to the common DQ2.5-restricted T-cell epitopes. (nih.gov)
  • Notwithstanding the heterogeneity of T cell epitopes in gluten, a few epitopes appear to account for most of the α-gliadin-specific recognition by CD4 + T cells from patients ( 8 , 9 ). (sciencemag.org)
  • In this study, we describe the mapping of two novel T cell epitopes of γ-gliadin and the experimental identification of the DQ2.5 binding register of these and three other γ-gliadin epitopes. (jimmunol.org)
  • The alignment of the experimentally determined binding registers of nine gluten epitopes reveal positioning of proline residues in positions P1, P3, P6, and P8 but never in positions P2, P4, P7, and P9. (jimmunol.org)
  • Interestingly, the DQ2.2 presentation for most epitopes is less efficient than presentation by the DQ2.5 molecule, and this is particularly prominent for the α-gliadin epitopes. (jimmunol.org)
  • Contrary to previous findings, our data do not show selective presentation of DQ2.5 over DQ2.2 for gluten epitopes that carry proline residues at the P3 position. (jimmunol.org)
  • Mechanism of Degradation of Immunogenic Gluten Epitopes from Triticum turgidum L. var. (asm.org)
  • The same results were found for other immunogenic epitopes, such as fragments 57-68 of α9-gliadin, 62-75 of A-gliadin, and 134-153 of γ-gliadin. (asm.org)
  • The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level. (immufood.com)
  • In many human leukocyte antigen (HLA) DQ2 (or DQ8)-positive individuals, exposure of the small intestine to gluten induces an inflammatory response, leading to destruction of the villous structure of the intestine ( 1-3 ). (sciencemag.org)
  • The effects of B. fragilis strains on Caco-2 cell culture permeability and inflammatory response to digested gliadin were determined. (asm.org)
  • Cellular immune responses to gluten were enhanced in peripheral blood mononuclear cells of type 1 diabetic patients ( 13 ). (diabetesjournals.org)
  • It was reported that oats were well tolerated clinically, and did not cause histological damage 6- 9 or induce cellular or humoral immune responses. (bmj.com)
  • The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread. (patentsencyclopedia.com)
  • In order to ensure the bioactivity of the SOD enzyme, a proprietary delivery system derived from gliadin was developed to protect the antioxidant from stomach acids on its way to the small intestine where it is absorbed by the body. (glisodinskin.com)
  • Furthermore, ex vivo challenge of biopsies from treated CD patients with gluten and with CD-associated bacteria induced an IL-17A response. (diva-portal.org)
  • Similarly, biopsies from normal controls did not respond to PT gliadin or PT avenin stimulation. (bmj.com)
  • CD4 + T cells reactive with the gliadin and glutenin subcomponents of gluten can be readily isolated from small intestinal biopsies of CD patients (but not of controls), and these cells are exclusively restricted by the disease-associated DQ2.5 or DQ8 HLA molecules. (jimmunol.org)
  • Gluten‐reactive CD4+ T cells are key players as pathogenic T helper cells. (els.net)
  • 2010) HLA‐DQ2‐restricted gluten‐reactive T cells produce IL‐21 but not IL‐17 or IL‐22. (els.net)
  • It has been suggested that TG2-reactive B cells are activated by gluten-reactive T cells following receptor-mediated uptake of TG2-gluten complexes. (jimmunol.org)
  • The disease is strongly associated with the HLA variant DQ2.5 ( DQA1*05 , DQB1*02 ), and intestinal gluten-reactive T cells from DQ2.5-positive patients are uniquely restricted by this HLA molecule. (jimmunol.org)
  • The activation of these gluten-reactive intestinal T cells probably represents a key event in the development of CD ( 1 ). (jimmunol.org)
  • Four models of how activation of TG2 specific B cells is facilitated by TG2 crosslinking and the help of gluten reactive CD4 T cells are proposed. (europa.eu)
  • More patients than ever are entering clinics with self-diagnoses of various reactions to gluten, leaving practitioners to decipher the intricacies of gluten-induced symptoms. (townsendletter.com)
  • Historically, one of the greatest impediments to accurate assessment and treatment of gluten-induced symptoms was the lack of a standardized diagnostic criteria for food allergy in general. (townsendletter.com)
  • Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. (sciencemag.org)
  • To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. (sciencemag.org)
  • Complementary electrophoretic, chromatography, and mass spectrometry techniques were used to characterize the gluten and epitope hydrolysis. (asm.org)