A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL1 RECEPTORS and the KIR2DL3 RECEPTORS.
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.
A KIR receptor that has specificity for HLA-C ANTIGEN. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTORS and the KIR2DL3 RECEPTORS.
A KIR receptor that has specificity for HLA-A3 ANTIGEN. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.
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.
A KIR receptor that has specificity for HLA-B ANTIGENS. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.
Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).
An activating KIR receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a short cytoplasmic tail.
A KIR receptor that has specificity for HLA-G antigen. It contains D0 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.
A large family of cell surface receptors that bind conserved molecular structures (PAMPS) present in pathogens. They play important roles in host defense by mediating cellular responses to pathogens.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
A subclass of NK cell lectin-like receptors that associates with members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY D to form heterodimeric receptors for HLA-E antigen.
Cytosolic signaling adaptor proteins that were initially discovered by their role in the innate immunity (IMMUNITY, INNATE) response of organisms that lack an adaptive immune system. This class of proteins contains three domains, a C-terminal ligand recognition domain, an N-terminal effector-binding domain, and a centrally located nuclear-binding oligomerization domain. Many members of this class contain a C-terminal leucine rich domain which binds to PEPTIDOGLYCAN on the surface of BACTERIA and plays a role in pathogen resistance.
The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.
A mitosporic fungal genus commonly isolated from soil. Some species are the cause of wilt diseases in many different plants.
The inherent or induced capacity of plants to withstand or ward off biological attack by pathogens.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
Diseases of plants.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
A mitosporic Loculoascomycetes fungal genus including some economically important plant parasites. Teleomorphs include Mycosphaerella and Venturia.
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.
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).
The interactions between a host and a pathogen, usually resulting in disease.
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.
A pattern recognition receptor that binds DOUBLE-STRANDED RNA. It mediates cellular responses to certain viral pathogens.
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.
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.
A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.
A species of gram-negative, fluorescent, phytopathogenic bacteria in the genus PSEUDOMONAS. It is differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
A subclass of NK cell lectin-like receptors that associates with a variety of members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY C to form heterodimeric receptors for HLA-E antigen.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
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.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
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.)
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.
Glycoproteins found on the membrane or surface of cells.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
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.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
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).
Established cell cultures that have the potential to propagate indefinitely.
Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A pattern recognition receptor that binds FLAGELLIN. It mediates cellular responses to certain bacterial pathogens.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
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.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Methods used by pathogenic organisms to evade a host's immune system.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
A plant species of the family SOLANACEAE, native of South America, widely cultivated for their edible, fleshy, usually red fruit.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
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.
PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Transport proteins that carry specific substances in the blood or across cell membranes.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
An encapsulated lymphatic organ through which venous blood filters.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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).
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.
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.
Mechanisms of action and interactions of the components of the IMMUNE SYSTEM.
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.
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.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Substances that are recognized by the immune system and induce an immune reaction.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
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.
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.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
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.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
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.
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.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Sites on an antigen that interact with specific antibodies.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Resistance to a disease agent resulting from the production of specific antibodies by the host, either after exposure to the disease or after vaccination.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Substances elaborated by bacteria that have antigenic activity.
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).
Elements of limited time intervals, contributing to particular results or situations.
Biologically active substances whose activities affect or play a role in the functioning of the immune system.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
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.
Exuberant inflammatory response towards previously undiagnosed or incubating opportunistic pathogens. It is frequently seen in AIDS patients following HAART.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Antibodies produced by a single clone of cells.
Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
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.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
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.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
The theory that T-cells monitor cell surfaces and detect structural changes in the plasma membrane and/or surface antigens of virally or neoplastically transformed cells.
The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (ANTIGENS, CD28) and CD80 antigens (ANTIGENS, CD80).
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
The number of LYMPHOCYTES per unit volume of BLOOD.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A classification of lymphocytes based on structurally or functionally different populations of cells.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Substances elaborated by viruses that have antigenic activity.
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.
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors. Antigen Lippincott's Illustrated ... An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane, which binds to a substance (for example ... The main receptors in the immune system are pattern recognition receptors (PRRs), Toll-like receptors (TLRs), killer activated ... ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 20 immunologic+receptor at the US National Library of Medicine Medical Subject ...
Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) that, in essence, put the brakes on NK cells. ... NOD-like receptor. References[edit]. *^ a b c d e f Janeway C, Travers P, Walport M, Shlomchik M (2001). Immunobiology (Fifth ... The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune ... Immune evasion[edit]. Cells of the innate immune system prevent free growth of microorganisms within the body, but many ...
KIR: short for Killer-cell Immunoglobulin-like Receptor, is a receptor for MHC Class I molecules on Natural Killer cells. ... A2AR: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune ... Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the ... B7-H3's receptors have not yet been identified. B7-H4: also called VTCN1, is expressed by tumor cells and tumor-associated ...
The KIR proteins are thought to play an important role in regulating of the immune responses. The HLA molecules are human ... KIR proteins with long tailed cytoplasmic domains transduce the inhibitory signals upon the ligand binding via an immune ... The KIR genes are polymorphic, which means that they have many different alleles. The KIR genes are also extremely homologous, ... including immunoglobulin-like killer cell receptors (KIR) that predominantly recognize antigens of class I human leukocyte ...
Immune receptor. The main receptors in the immune system are pattern recognition receptors (PRRs), toll-like receptors (TLRs), ... KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors.[12] ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... receptors, G protein-linked (metabotropic) hormone receptors, and enzyme-linked hormone receptors.[1] Intracellular receptors ...
KIR and CD94 (CTLR) receptors are expressed by 5% of peripheral blood T cells. KIR receptors are named based on the number of ... Natural killer (NK) cells are a type of lymphocyte cell involved in the innate immune system's response to viral infection and ... Group A only has one activating KIR receptor, whereas Group B contains many activating KIR receptors, and as a result group B ... In the human fetal liver, KIR and CD49 receptors are already expressed by NK cells, indicating that at least some KIR receptors ...
Many ITIM-bearing receptors recruit SHP-1 and/or SHP-2 including KIRs, ILT, Ly49, LAIR-1, CD22, CD72 and Signal Regulatory ... ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of ... ITIM-containing receptors often serve to target Immunoreceptor tyrosine-based activation motif(ITAM)-containing receptors, ... ITIM conserved sequence was first identified in the low affinity IgG receptor FcγRIIB. All ITIM containing receptors are a part ...
... leukocyte inhibitory receptor; MIR: macrophage inhibitory receptor. Brown, D.; Trowsdale, J.; Allen, R. (2004). "The LILR ... Carrington, M; Norman, P (2003). The KIR Gene Cluster (e-book). NCBI Bookshelf.. ... family: modulators of innate and adaptive immune pathways in health and disease". Tissue Antigens. 64 (3): 215-225. doi:10.1111 ... leukocyte immunoglobulin-like receptor; ILT: immunoglobulin-like transcript; LIR: ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... KIR proteins are thought to play an important role in regulation of the immune response. "Human PubMed Reference:". National ... "Distribution of killer cell immunoglobulin-like receptor (KIR) genotypes in patients with familial Mediterranean fever". ... The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb ...
Signals transmitted through the IL-12 receptor combined with CD2 and MHC class I-binding receptor provide a three-prong ... "NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs ... Sun JC, Beilke JN, Lanier LL (January 2009). "Adaptive immune features of natural killer cells". Nature. 457 (7229): 557-61. ... KIR-ligand mismatch has a beneficial effect on the alloreactivity of donor NK cells against recipient leukemia. Besides, it has ...
Receptors of KIR (Killer-cell immunoglobulin-like receptor) family bind concrete MHC class I molecules. If the graft has these ... 21(5): 557-562 Walker WE, Goldstein DR (August 2007). "Neonatal B cells suppress innate toll-like receptor immune responses and ... KIR receptors provide inhibitory signal). So if these ligands are missing, there is no inhibitory signal and NK cell becomes ... which happens when the immune tolerance of pregnancy is impaired. In many instances the maternal immune system attacks the ...
Use of an inhibitor that blocks the interaction of PD-L1 with the PD-1 receptor can prevent the cancer from evading the immune ... KIR, OX40, PARP, CD27, and ICOS. Pembrolizumab (formerly MK-3475 or lambrolizumab, Keytruda) was developed by Merck and first ... Postow MA, Sidlow R, Hellmann MD (January 2018). "Immune-Related Adverse Events Associated with Immune Checkpoint Blockade". ... Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer. PD-1 and PD-L1 inhibitors act ...
... the only identified receptors for S1P are the high-affinity G protein-coupled receptors (GPCRs), also known as S1P receptors ( ... PIP2 was shown to directly agonizes Inward rectifying potassium channels(Kir). In this regard intact PIP2 signals as a bona ... and several immune complexes. S1P is probably formed at the inner leaflet of the plasma membrane in response to TNFα and other ... This signaling lipid has great affinity for the GRP55 receptor and the PPAR alpha receptor. It has been identified as an anti- ...
... (KAR) and Killer Inhibition Receptors (KIRs). Both type of receptors act together to activate or not ... TAK W., Mak; SAUNDERS, Mary (2010). Primer to the Immune Response: Academic Cell Update Edition. Academic Press. pp. 174, 176, ... Killer Activation Receptors) and the NK KIRs (meaning: Killer Inhibitory Receptors). Such receptors have a broad binding ... The KIR term has been started to be being used parallelly both for the Killer-cell immunoglobulin-like receptors (KIRs) and for ...
Pilsbury LE, Allen RL, Vordermeier M (2010). "Modulation of Toll-like receptor activity by leukocyte Ig-like receptors and ... Brown D, Trowsdale J, Allen R (September 2004). "The LILR family: modulators of innate and adaptive immune pathways in health ... "Plasticity in the organization and sequences of human KIR/ILT gene families". Proceedings of the National Academy of Sciences ... "Leukocyte receptor complex-encoded immunomodulatory receptors show differing specificity for alternative HLA-B27 structures". ...
CB2 receptors are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. ... Kir or IRK). However, a much more complex picture has appeared in different cell types, implicating other potassium ion ... Cannabinoid receptors are of a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of ... Cannabinoid receptor type 1 (CB1) receptors are thought to be one of the most widely expressed Gαi protein-coupled receptors in ...
Inhibitory receptors[edit]. *Killer-cell immunoglobulin-like receptors (KIRs) belong to a multigene family of more recently ... Natural killer cells, or NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells ... activating receptors and inhibitory receptors, including killer-cell immunoglobulin-like receptors. Most of these receptors are ... Most KIRs are inhibitory and dominant. Regular cells express MHC class 1, so are recognised by KIR receptors and NK cell ...
Most KIRs are inhibitory and dominant. Regular cells express MHC class 1, so are recognised by KIR receptors and NK cell ... This example of immune evasion actually highlights NK cells' importance in tumor surveillance and response, as CD8 cells can ... activating receptors and inhibitory receptors, including killer-cell immunoglobulin-like receptors. Most of these receptors are ... NK cell receptors can also be differentiated based on function. Natural cytotoxicity receptors directly induce apoptosis (cell ...
The receptor is expressed on monocytic cells and transduces a negative signal that inhibits stimulation of an immune response. ... 2000). "Plasticity in the organization and sequences of human KIR/ILT gene families". Proc. Natl. Acad. Sci. U.S.A. 97 (9): ... 2000). "Genomic organization of the human leukocyte immunoglobulin-like receptors within the leukocyte receptor complex on ... "Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor ...
Her main areas of research currently are into interactions between maternal Killer-cell Immunoglobulin-like Receptor (KIR) and ... Moffett has come out strongly against the use of immune-suppressive drugs as a means of preventing miscarriage, commenting, " ... This work revealed how these cells communicate and modulate the mother's immune response during the first trimester of ... These genes are involved in chemical signalling between placenta trophoblast cells and natural killer immune cells. In 2018, ...
If the KIR receptors of NK cell find their cognate antigen on the surface of target cell, formation of the lytic synapse is ... The immune synapse is also known as the supramolecular activation cluster or SMAC. This structure is composed of concentric ... In this process, the killer-cell immunoglobulin-like receptors (KIRs) containing long cytoplasmic tails with immunoreceptor ... The process of formation begins when the T-cell receptor (TCR) binds to the peptide:MHC complex on the antigen-presenting cell ...
KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer-cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ... "Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors". Nature. 389 (6646): 96 ...
KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... 2002). "Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations". Genes ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ...
KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ... The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb ...
"NK cell receptor gene of the KIR family with two IG domains but highest homology to KIR receptors with three IG domains". ... KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ...
KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... 2001). "Recognition of HLA-Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ...
KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important ... "Development of a PCR-SSOP approach capable of defining the natural killer cell inhibitory receptor (KIR) gene sequence ...
NKG2A NKG2B NKG2C NKG2D NKG2E NKG2H Activating KIRs KIR2DS1 Killer inhibitory receptors (KIRs) Two domains, long cytoplasmic ... Geijtenbeek TB, Gringhuis SI (July 2009). "Signalling through C-type lectin receptors: shaping immune responses". Nat. Rev. ... Anaphylatoxin receptors C3a receptor C5a receptor (CD88) C5AR2 Fc receptor Fc-gamma receptors (FcγR) FcγRI (CD64) FcγRIIA ( ... Prolactin receptor) Type II cytokine receptor - Lack WSXWS motif Interferon receptors Interferon-α/β receptor (IFNAR) - ...
... and killer immunoglobulin-like receptors (KIRs). Notably, mouse models suggest that they lack CD16 and L-selectin, proteins ... However, unlike NK cells, uNK's do not have a fundamental role in the innate immune system and therefore, are not cytotoxic. ... These cells are attracted to the uterus during pregnancy independent of chemokine receptors CCR-2 and CCR-5 in spite of these ... Human uNKs share many of the surface receptors and proteins of circulating Natural Killer (cNK) cells, exhibiting high levels ...
Immune receptor. The main receptors in the immune system are pattern recognition receptors (PRRs), toll-like receptors (TLRs), ... KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors.[12] ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... receptors, G protein-linked (metabotropic) hormone receptors, and enzyme-linked hormone receptors.[1] Intracellular receptors ...
"Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate". Science. 310 (5756): 1970-1973. PMID 16373579.. ... Kompleks antigen diri MHC itu dikenali oleh reseptor imunoglobulin sel pembunuh (KIR) yang menahan aktivitas sel NK.[54] ... "Immunobiology: The Immune System in Health and Disease. 5th edition (dalam bahasa Inggris).. ... R.M. Suskind, C.L. Lachney, J.N. Udall, Jr., "Malnutrition and the Immune Response", in: Dairy products in human health and ...
... killing cell Immunoglobulin Receptors) (KIR) மூலமாக அங்கீகரிக்கப்படுகின்றன, அதன் அடிப்படையில் கொல்லும் செல்களில் தடைகளை ... நோய் எதிர்ப்பாற்றல் முறைமை (Immune system) என்பது, நோய்களை உருவாக்கும் நுண்ணுயிரிகள் முதலானவற்றை அடையாளம் கண்டு அழிப்பதன் மூலம் ... Immune tolerance in pregnancy) · நோயெதிர்ப்புக் குறைபாடு (Immunodeficiency) · ...
P. Sharma, J. P. Allison: Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. ... GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations.. . In: Eur J Immunol. ... KIR, LAG3,[7] PD-1,[8] TIM-3[9] und VISTA (V-domain Ig suppressor of T cell activation).[10] ... A. Śledzińska, L. Menger, K. Bergerhoff, K. S. Peggs, S. A. Quezada: Negative immune checkpoints on T lymphocytes and their ...
The encoded protein may associate with the killer cell immunoglobulin-like receptor (KIR) family of membrane glycoproteins and ... from immune cells to bone modeling and brain myelination". J. Clin. Invest. 111 (3): 313-4. doi:10.1172/JCI17745. PMC 151875. ... Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Two alternative transcript ... Lanier LL, Corliss B, Wu J, Phillips JH (1998). "Association of DAP12 with activating CD94/NKG2C NK cell receptors". Immunity. ...
KIR patterns on maternal natural killer cells of the mother and KIR ligands on the fetal cells could have an effect on ... After giving birth, about 50-75% of women carry fetal immune cell lines. Maternal immune cells are also found in the offspring ... most mother's fetal-specific CD8+ T cells undergo clonal deletion and express low levels of chemokine receptors and ligands - ... preferentially differentiating to Treg cells and preventing a fetal immune response to maternal antigens. This expanded immune ...
KIR), natural cytotoxicity receptors (NCR), and critical adhesion molecules. (Medical Immunology, p. 122) Dendritic cell is ... Yet they are much more closely related to T cells (part of the adaptive immune system) than to other cells of the innate immune ... Immuno-Biology, The Immune System in Health and Science. Fundamental Immunology 5th edition Immuno-Biology, The Immune System ... These 'non-MHC restricted T cells' are involved in specific primary immune responses, tumor surveillance, immune regulation and ...
Because KIR and HLA genes are inherited independently, the ideal donor can have compatible HLA genes and KIR receptors that ... It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias ... which interact with KIR receptors. NK cells are within the first cells to repopulate host's bone marrow which means they play ... Falco M, Pende D, Munari E, Vacca P, Mingari MC, Moretta L (April 2019). "Natural killer cells: From surface receptors to the ...
The complex HLA-F/HLA class-I OC is a ligand for a subset of KIR (Killer-cell immunoglobulin-like receptor) receptors. ... Upon immune cell activation, HLA-F binds free forms of HLA class I molecules and reaches the cell surface as heterodimer. In ... it is a ligand for KIR receptors and can both activate and inhibit KIR; second, it is involved in cross-presentation of ... Specifically, it was demonstrated that HLA-F interacts physically and functionally with three KIR receptors: KIR3DL2, KIR2DS4, ...
... is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by ... the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial ... Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. ... KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon ...
Killer immunoglobulin-like receptors (KIRs) are proteins that control how activated part of the immune system can become. KIRs ... Their donors will have KIR testing, and if possible, patients donors will be chosen based on KIR typing. (Patients whose ... In this study, researchers want to see if this is the case for haploidentical donors: They want to learn if certain KIR genes ... A Study Assessing Stem Cell Transplantation from a Half-Matched Related Donor, Using KIR Genes as well as Other Factors to ...
Killer cell immunoglobulin-like receptors are associated with common variable immune deficiency pathogenesis. J Allergy Clin ... A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three ... Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell ... Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role ...
... immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy. ... KIR), killer cell lectin type receptors (KLR), and natural cytotoxic receptors (NCR) as well as immunoglobulin Fc receptors ( ... Chemokine Receptors on Blood and NK-Cells. Conventional and NK-cells present in the normal PB have different CKR repertoires ( ... 3.1.2. Chemokine Receptors on Conventional NK-Cells. In contrast to NK-cells, the majority of the NK-cells are CXCR1/CXCR2− and ...
Recent studies revealed that complex integration of NK receptor signaling controls cytoskeletal rearrangement and other immune ... Recent studies revealed that complex integration of NK receptor signaling controls cytoskeletal rearrangement and other immune ... NKp46 is a major NK cell-activating receptor that is involved in the elimination of target cells. NK cells form different types ... NKp46 is a major NK cell activating receptor that is involved in the elimination of target cells. NK cells form different types ...
Buy the Paperback Book Mechanisms of Lymphocyte Activation and Immune Regulation X by Sudhir Gupta at Indigo.ca, Canadas ... An Evolutionarily Conserved Mediator of Immune and Inflammatory Responses.- Influence of KIR Diversity on Human Immunity.- ... Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense, and Autoimmunity.- Role of Complement Receptor ... Mechanisms of Lymphocyte Activation and Immune Regulation X: Innate Immunity. EditorSudhir Gupta, William E. Paul, Ralph ...
HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, ... HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, ... HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, ... HLA and KIR Associations of Cervical Neoplasia. Bao, Xiao; Hanson, Aimee L.; Madeleine, Margaret M.; Wang, Sophia S.; Schwartz ...
Checkpoint receptors on NK cells: breaking barriers. Immune checkpoint receptors are a group of inhibitory receptors that ... 8, 9). Inhibitory receptors, such as killer-cell immunoglobulin-like receptors (KIRs), deliver negative signals that prevent NK ... KIRs and other inhibitory receptors recognize MHC I molecules, whose absence may result in NK activation, the so-called " ... The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 2005;436(7054):1186-1190.. View ...
Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite ... specificity of KIR-HLA interactions in human health and disease.. Authors. Maureen P. Martin, Vivek Naranbhai, Patrick R. Shea ... Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. ... Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. ...
HLA and KIR Region Genomics in Immune-Mediated Diseases (U19) RFA-AI-14-013. NIAID ... immunoglobulin-like receptor (KIR) genomic regions and (1) immune-mediated diseases, including risk and phenotype, and (2) cell ... receptor (KIR) genetic regions and immune-mediated diseases, including outcomes following cell, tissue, and organ ... KIRs are encoded by a highly polymorphic gene cluster on chromosome 19, and have evolved to catalyze swift immune responses to ...
Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) that, in essence, put the brakes on NK cells. ... NOD-like receptor. References[edit]. *^ a b c d e f Janeway C, Travers P, Walport M, Shlomchik M (2001). Immunobiology (Fifth ... The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune ... Immune evasion[edit]. Cells of the innate immune system prevent free growth of microorganisms within the body, but many ...
Using a new technique to identify bone marrow donors who make the most potent cancer-fighting immune cells, the risk of death ... KIR is short for killer-cell immunoglobulin-like receptor. KIR proteins regulate NK cells. ... Using a new technique to identify bone marrow donors who make the most potent cancer-fighting immune cells, the risk of death ... Researchers Develop New Technique That Can Identify Bone Marrow Donors Making The Most Potent Cancer-fighting Immune Cells. ...
The Killer Immunoglobulin-like Receptors (KIRs) are a family of highly variable receptors which regulate cytotoxicity of ... Unraveling the genetic expression of the highly variable immune receptors of a killer. Supervisors. T.W. Kuijpers. ... The KIR genes, clustered on the genome in the KIR locus, are distributed unequally across the population due to variation in ... all contribute to the complexity of KIR expression in humans. In addition, Interleukin-15 seems to be a potent regulator of KIR ...
Long EO (1999) Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875-904CrossRefGoogle Scholar ... Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201-214CrossRefGoogle ... Biassoni R, Malnati MS (2018) Human natural killer receptors, co-receptors, and their ligands. Curr Protoc Immunol 121(1):e47 ... Middleton D, Faviel G (2009) The extensive polymorphism of KIR genes. Immunol 129:8-19CrossRefGoogle Scholar ...
NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome. ... CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation. ... Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK ... Activating KIRs on Educated NK Cells Support Downregulation of CD226 and Inefficient Tumor Immunosurveillance. ...
NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome. ... CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation. ... KIR gene mismatching and KIR/C ligands in liver transplantation: consequences for short-term liver allograft injury. ... Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK ...
... there was a greater proportion of KIRs in clusters. Upon receptor triggering, a structured interface called the immune synapse ... investigated the effects of genetic diversity in KIR-encoding genes on receptor organization and activity. They found that KIRs ... Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs ... These cells express several germline-encoded inhibitory receptors (KIRs) that prevent NK cells from killing healthy cells but ...
NK cell receptors (NKRs). The killer cell immunoglobulin-like receptor (KIR) family of NKRs comprises 2 functionally distinct ... SNPs in non-HLA genes can influence immune responses. Genes subject to CNV include MHC, KIR, and the genes encoding Fc and ... Natural killer (NK) cells are innate immune lymphocytes that recognize self-MHC class I through a unique class of receptors, ... KIR genotype is the dominant factor determining the repertoire of KIR expression on NK cells, that is, the influence of HLA ...
In this Review, we discuss findings relating to the interactions of CTCs and DTCs with the immune system, in the context of ... During this process, the tumour cells are open to attack by the immune system. This Review highlights the possible mechanisms ... Given the expanding role of immunotherapies in the treatment of cancer, interactions between tumour cells and immune cells are ... or subvert the immune system in order to survive and form metastatic lesions. Metastatic spread of tumour cells is the main ...
In AML, MHC Class I loss is rare, but allows NK cells to escape through killer cell immunoglobulin-like receptors (KIR). ... 5. MSCs and Tumor Immune Escape. 5.1. Immune System in Myeloid Malignancies: A Naive Surveillant?. Innate and adaptive immune ... with a double receptor for the AML blast and one recruiting NKs. Immune reconstitution has a key role in enabling immune- ... showed that tumor microenvironment suppresses chimeric antigen receptor T (CART) cell activity through IDO immune escape in a ...
Additional lymphocyte co-regulators, including LAG3, TIM3, NKG2/2D, and the KIR family receptors. ... TIM3: A receptor present on the surface of T cells that triggers helper T cell apoptosis, promoting immune tolerance. It is ... LAG3: A receptor present on the surface of both regulatory T cells (activates their anti-immune function) and cytotoxic T cells ... BTLA: A receptor present on T cells that dampens the immune response by reducing T cell population growth and decreasing ...
KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors. Antigen Lippincotts Illustrated ... An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane, which binds to a substance (for example ... The main receptors in the immune system are pattern recognition receptors (PRRs), Toll-like receptors (TLRs), killer activated ... ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 20 immunologic+receptor at the US National Library of Medicine Medical Subject ...
Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) which essentially put the brakes on NK cells.[ ... 4 Innate immune system *4.1 Pattern recognition by cells *4.1.1 Toll-like receptors ... Innate immune cells express pattern recognition receptors (PRRs) which recognize components that are conserved among broad ... In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive ...
... receptors engaged upon interaction with target cell surface ligands ... 2014) Ly49 receptors: innate and adaptive immune paradigms. Frontiers in Immunology 5: 145. ... 2012) A phase 1 trial of the anti‐KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood 120: 4324- ... 2008) Human microRNAs regulate stress‐induced immune responses mediated by the receptor NKG2D. Nature Immunology 9 (9): 1065- ...
Receptor systems recently or currently under study include the KIR and the TREM and TREM-Like Receptors. Recent findings have ... Receptor-Mediated Regulation of the Innate Immune System. Our laboratory studies the molecular regulation and function of ... and TREM-Like Receptors. One of the best-characterized myeloid DAP12-coupled receptor systems are the triggering receptors ... The Killer Ig-Like Receptors (KIR) of NK Cells. A second interest of the lab is centered on unraveling the regulation of NK ...
A single receptor on natural killer cells recognizes an amino acid sequence conserved across Zika, dengue, and related ... can be activated by cell-surface receptors called activating KIRs. GWENOLINE BORHIS ... Immune System Targets Diverse Viruses Using the Same Small Peptide. A single receptor on natural killer cells recognizes an ... Strategies for Smuggling Gene Therapies Past the Immune System. Strategies for Smuggling Gene Therapies Past the Immune System ...
Class: immune system. Keywords: MHC, HLA, class I, KIR, NK cell receptor, Immunoglobulin fold, receptor/MHC complex, IMMUNE ... Compound: natural killer cell receptor kir2dl2. Species: Homo sapiens [TaxId:9606]. Database cross-references and differences ( ... Compound: natural killer cell receptor kir2dl2. Species: Homo sapiens [TaxId:9606]. Database cross-references and differences ( ... Description: structure of a complex between the human natural killer cell receptor kir2dl2 and a class I MHC ligand hla-cw3. ...
Conversely, blockade of inhibitory receptor pathways can be exploited to improve immune responses. KIR blockade is being tested ... whereas human receptors endowed with the corresponding function were Ig-like (killer Ig-like receptors, or KIRs) (4-7). Gene ... KIR. killer Ig-like receptor. SH2. Src homology 2. SHP. Src homology 2 domain-containing phosphatase.. ... The receptor inhibition model became widely accepted following the molecular identification of an NK cell receptor that ...
KIR and ILTs modulate activation of other immune receptors. Inhibitory ILTs can suppress Fc receptor or TCR signaling on ... HLA-B27 FHC bind to a KIR receptor. Having shown that an FHC form of HLA-B27 can engage ILT receptors we then studied its ... This includes two families of class I-specific regulatory receptors-the killer cell Ig receptors (KIR)3 and the Ig-like ... stochastic expression of individual KIR in a given clone. Referred to as NK receptors, KIR are also expressed on subsets of CD4 ...
... dominant inhibitory signals are transduced by Killer Immunoglobulin Like Receptors (KIR) recognizing cognate HLA class I on ... Overcoming this barrier to immune surveillance, multiple approaches to enhance NK-mediated responses are being investigated ... These stimulatory pathways are counterbalanced by inhibitory receptors that raise NK cell activation threshold through negative ... cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. ...
  • They require co-stimulation via NKG2D, 8 suggesting that the interaction of NKG2D with its ligands may play a role in shaping the immune response within the gut. (nature.com)
  • The cytotoxic activity of the NK-cells is controlled by the balance between inhibitory and activating receptors, whose ligands are self-Major Histocompatibility Complex (MHC) class I molecules and molecules expressed on stressed, viral infected, and tumor cells. (hindawi.com)
  • Instead, their activation is controlled by a repertoire of germ-line encoded activating receptors that recognize different ligands on the surface of susceptible target cells. (frontiersin.org)
  • HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. (lu.se)
  • Biassoni R, Malnati MS (2018) Human natural killer receptors, co-receptors, and their ligands. (springer.com)
  • Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing. (nih.gov)
  • Natural killer (NK) cell effector functions are regulated by integrated signals across the array of stimulatory and inhibitory receptors engaged upon interaction with target cell surface ligands. (els.net)
  • More understanding of the nature of interaction of NK cell receptors and their ligands as well as the regulation mechanisms should facilitate the development of effective therapy. (els.net)
  • The activity of NK cells is regulated by the delicate balance of signals from inhibitory and stimulatory cell surface receptors engaged upon interaction with their ligands. (els.net)
  • Deng L and Mariuzza RA (2006) Structural basis for recognition of MHC and MHC‐like ligands by natural killer cell receptors. (els.net)
  • El‐Gazzar A, Groh V and Spies T (2013) Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer. (els.net)
  • HLA class I are ligands for members of the killer Ig receptor (KIR) and Ig-like transcript (ILT)/LIR/LILR families (the new LILR nomenclature is described at www. (jimmunol.org)
  • Class I also act as ligands for immunomodulatory receptors, particularly those encoded within the leukocyte receptor complex on chromosome 19. (jimmunol.org)
  • Recognition and killing of aberrant, infected or tumor targets by Natural Killer (NK) cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. (frontiersin.org)
  • More recently, activating KIR came into the spotlight for their potential ability to directly activate donor NK cells through in vivo recognition of HLA or other ligands. (frontiersin.org)
  • This Research Topic welcomes contributions addressing mechanisms of NK-mediated activation in response to disease as well as past and contemporary strategies to enhance NK-mediated reactivity through control of the interactions between NK receptors and their ligands. (frontiersin.org)
  • HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors. (springer.com)
  • While numerous receptors are found in most cells, each receptor will only bind with ligands of a particular structure, much like how locks will only accept specifically shaped keys. (wikipedia.org)
  • Nuclear receptors - While they are called nuclear receptors, they are actually located in the cytoplasm and migrate to the nucleus after binding with their ligands. (wikipedia.org)
  • Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. (cdc.gov)
  • Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. (cdc.gov)
  • The ligands for several KIR proteins are subsets of HLA class I molecules. (wikipedia.org)
  • Target cell killing depends on the engagement of specific activating receptors and coreceptors expressed at the NK cell surface with surface ligands expressed on target cells. (aacrjournals.org)
  • The majority are orphan receptors because their cellular ligands are still elusive. (aacrjournals.org)
  • Indeed, engagement of activating NK cell receptors by ligands expressed on tumor cells can overcome inhibitory signals and stimulate NK cell responses even in the presence of autologous MHC class I ( 6 , 7 ). (aacrjournals.org)
  • This mechanism is efficiently counteracted in many human tumors, where cells evade NK cell-mediated killing by shedding or intracellular retention of ligands for activating receptors ( 8 ). (aacrjournals.org)
  • To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU) patients were determined. (jove.com)
  • Here we report that collagens are high affinity ligands for the broadly expressed inhibitory leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). (rupress.org)
  • We now show that collagens are functional ligands for LAIR-1 and directly inhibit immune cell activation in vitro. (rupress.org)
  • Thus far, all documented ligands for immune inhibitory receptors are membrane molecules, implying a regulatory role in cell-cell interaction. (rupress.org)
  • Notably, HLA class I molecules serve as ligands for innate immune receptors, including the killer cell immunoglobulin-like receptors (KIR) and the leukocyte immunoglobulin-like receptors (LILR) encoded by genes located in the Leukocyte Receptor Complex (LRC). (cancer.gov)
  • Due to the extensive diversity of the HLA, KIR, and LILR gene loci and their roles in both the innate and adaptive immune response, variation at these loci impacts the risk of disease pathogenesis, and co-evolution of the unlinked genes encoding these receptors and their ligands must occur in order to maintain an appropriate level of functional interaction that is beneficial to the individual. (cancer.gov)
  • Apart from their role in the acquired immune response, HLA class I molecules participate in innate immunity as ligands for the killer immunoglobulin-like receptors (KIR). (ragoninstitute.org)
  • Table 1 lists examples of positive and negative immune checkpoint receptors and their ligands. (bio-rad-antibodies.com)
  • One of the major endocannabinoid ligands that activate cannabinoid receptors, 2-arachidonyl glycerol (2-AG), is produced by DAG lipases (2). (cellsignal.com)
  • A downregulation of MHC class I on damaged cells, or a mismatch between inhibitory subgroups of killer immunoglobulin-like receptors (KIR) and their respective human leukocyte antigen (HLA) ligands on cells will render targets susceptible to NK-cell killing ( 6, 7 ). (aacrjournals.org)
  • Panel includes major classes of cytokines and their receptors, enzymes with specific gene families such as the major chemokine ligands and receptors, interferons and their receptors, the TNF-receptor superfamily, and the KIR family genes. (nanostring.com)
  • In Hodgkin lymphoma, alterations of chromosome 9p24 that increase the expression of programed death receptor ligands 1 and 2 (PD-L1 and PD-L2) have been frequently identified and suggest that patients with HL may be uniquely positioned to derive benefit from program cell death receptor 1 (PD-1) blockade with immune checkpoint inhibitors. (onclive.com)
  • The HLA class I molecules also act as ligands for killer immunoglobulin receptors (KIR), which regulate the cytotoxic activity of natural killer (NK) cells. (chori.org)
  • Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. (prolekare.cz)
  • Controlling both NK cell development and effector function is a variety of interactions between NK cell receptors and their ligands [6] , the class I molecules of the major histocompatibility complex (MHC): called the HLA complex in humans. (prolekare.cz)
  • The KIR comprise a highly polymorphic, multi-gene family of receptors whose identified ligands belong to the human leukocyte antigen (HLA) class I family of molecules. (tcd.ie)
  • We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. (nature.com)
  • The family comprises 14 genes and two pseudogenes, although the number of loci varies on different KIR haplotypes. (nature.com)
  • Only four loci are common to all KIR haplotypes (the so-called 'framework' genes KIR2DL4 , -3DL1 , -3DL3 , and the pseudogene -3DP1 ), whereas the presence of remaining 'non-framework' loci can vary between haplotypes. (nature.com)
  • In this study, researchers want to see if this is the case for haploidentical donors: They want to learn if certain KIR genes in the half-matched donor will reduce cancer recurrence in the transplant recipient. (mskcc.org)
  • Patients whose donors do not have the beneficial KIR genes will still receive a transplant. (mskcc.org)
  • Researchers will determine if patients who received a transplant of stem cells from a donor with favorable KIR genes have a lower risk of cancer recurrence. (mskcc.org)
  • The KIR genes, clustered on the genome in the KIR locus, are distributed unequally across the population due to variation in gene presence and gene copy number. (uva.nl)
  • Middleton D, Faviel G (2009) The extensive polymorphism of KIR genes. (springer.com)
  • investigated the effects of genetic diversity in KIR-encoding genes on receptor organization and activity. (sciencemag.org)
  • They found that KIRs encoded by distinct genes were present at varying abundances and in clusters of varying sizes, which led to differences in downstream signaling that affected NK cell function. (sciencemag.org)
  • Together, these data suggest that genetic diversity in KIR-encoding genes affects receptor organization, signaling, and functional outcomes. (sciencemag.org)
  • Using superresolution microscopy, we found that inhibitory KIRs encoded by different genes and alleles were organized differently at the surface of primary human NK cells. (sciencemag.org)
  • This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes. (rupress.org)
  • The KIR2D genes encoding HLA-C receptors form part of a larger group of KIR called lineage III KIR ( 22 ). (rupress.org)
  • The KIR genes are polymorphic, which means that they have many different alleles. (wikipedia.org)
  • The KIR genes are also extremely homologous, which means that they are similar in position, structure and evolutionary origin, but not necessarily in function. (wikipedia.org)
  • The genes responsible for coding of KIR proteins are found along the 19th chromosome section 19q 13.4 within the 1Mb Leukocyte Receptor Complex (LRC). (wikipedia.org)
  • This usually occurs at loci such as immunoglobulin or T cell receptor (TCR) genes where a functional rearrangement among genes takes place. (tripod.com)
  • Potential genetic factors include HLA background, immune cytokine promoter and receptor polymorphisms, as well as polymorphisms in KIR and other cytotoxic T-cell-specific genes. (haematologica.org)
  • The genes can be highly polymorphic and encode for fundamentally important receptors for controlling the functional response of NK cells. (gla.ac.uk)
  • KIR genes are highly polymorphic and contribute vital variability to our immune system. (biomedcentral.com)
  • Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. (biomedcentral.com)
  • KIR gene family and other genes involved in virus immune defenses. (clinicaltrials.gov)
  • Both KIR and LILR genes encode inhibitory and activating molecules, which regulate immune cell activity through fine-tuned signaling pathways. (cancer.gov)
  • The KIR genes and haplotypes are exceptionally diverse and rapidly evolving (characteristics they share with the HLA loci). (cancer.gov)
  • Less is known about the LILR genes overall, but like KIR, some of the LILR genes are very polymorphic and the locus does have some degree of gene copy number variability. (cancer.gov)
  • Individual KIRs exhibit specificity for a given set of HLA class I molecules, so the presence of genes/alleles encoding corresponding receptor-ligand pairs is necessary for functional activity, but the presence of one without the other has no influence on effector cell activity. (cancer.gov)
  • Our approach involves direct testing for genetic effects of polymorphic immune response genes on specific disease outcomes followed by molecular or cellular biological approaches to understand the basis for the genetic association. (cancer.gov)
  • Thus the presence of genes/alleles encoding corresponding receptor-ligand pairs is necessary for functional activity, but the presence of one without the other has no influence on effector cell activity. (ragoninstitute.org)
  • Our approach involves direct testing for genetic effects of polymorphic genes within the MHC, as well as functionally relevant combinations of HLA class I alleles and KIR genes, on specific disease outcomes. (ragoninstitute.org)
  • This is an especially important consideration when studying genetic loci composed of multiple homologues that share functional activity, which both the HLA genes and the KIR genes exemplify, because it is a significant aid in identifying the actual disease locus amongst multiple logical candidates. (ragoninstitute.org)
  • Certain combinations of maternal KIR genes and fetal MHC genes are associated with pre-eclampsia, whereas other KIR genes appear to protect against the disease. (cam.ac.uk)
  • Moreover, all these SNPs were found within a group of genes known as the HLA (human leukocyte antigen) system, which encodes for proteins that play a vital role in the immune response. (elifesciences.org)
  • The Immuno Polymorphism Database (IPD) ( http://www.ebi.ac.uk/ipd/ ) is a set of specialist databases related to the study of polymorphic genes in the immune system. (springer.com)
  • The effect of LILRB1 but not LILRA3 gene polymorphism in immunopathology of ankylosing spondylitis-A parallel to KIR genes. (cdc.gov)
  • Objective This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3 . (bmj.com)
  • Design We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). (bmj.com)
  • The HLA genes, as well as the innate immune genes IFNL3 and KIR , are considered to be important determinants of viral outcomes, however, their interaction with each other has not been well studied. (bmj.com)
  • The Allele Frequency Net Database (AFND) is a public database which contains frequency information of several immune genes such as Human Leukocyte Antigens (HLA), Killer-cell Immunoglobulin-like Receptors (KIR), Major histocompatibility complex class I chain-related (MIC) genes, and a number of cytokine gene polymorphisms. (re3data.org)
  • These other genes are now known to include those encoding so-called killer-cell immunoglobulin-like receptors (KIR) as well as "natural killer" immune cells, which interact with HLA molecules, which some studies suggest impact outcomes of a grafted organ. (thermofisher.com)
  • 3] The turn are recognised by the TCR on CD8+ adaptive immune responses through binding classic HLA class I genes consist of eight T cel s. (who.int)
  • We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. (sciencemag.org)
  • The Human Leukocyte Antigen (HLA) genes located on chromosome 6 are responsible for regulating immune function via antigen presentation and are one of the determining factors for stem cell and organ transplantation compatibility. (pacb.com)
  • 84 genes involved with the anti-fungal immune response are also included. (nanostring.com)
  • Control of NK cell function is mainly regulated by is recognition of self MHC class I molecules through a set of inhibitory receptors - the killer-cell immunoglobulin-like receptors (KIRs) in humans and the Ly49 receptor family in mice ( 8 - 10 ). (frontiersin.org)
  • These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). (wikipedia.org)
  • Moretta A, Bottino C, Vitale M et al (1996) Receptors for HLA class-I molecules in human natural killer cells. (springer.com)
  • Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. (springer.com)
  • Parham P, Norman PJ, Abi-Rached L et al (2012) Human-specific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex class I molecules. (springer.com)
  • Inhibitory NK cell receptors for MHC class I molecules not only have a critical role in controlling NK cell responses but also confer the functional competence of NK cells in response to activation signals. (els.net)
  • Gene transfer experiments and transgenic mice demonstrated that single receptors of either type conferred both the specificity for MHC class I molecules and the capacity to prevent target cell lysis ( 8 , 9 ). (jimmunol.org)
  • NK cells express highly polymorphic killer cell immunoglobulin receptors (KIR's) that recognize specific HLA class I molecules. (jax.org)
  • In addition to the TCR, MHC class I molecules bind to immunoregulatory receptors including members of the killer immunoglobulin-like receptor (KIR) and leukocyte immunoglobulin-like receptor (LILR) families. (springer.com)
  • Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. (rupress.org)
  • In T cells, synapse formation appears to increase the density of relevant molecules in the target cell contact to ensure sufficient stimulation of the T cell receptor by the few relevant MHC/peptide complexes that are presented by the APCs ( 5 - 7 ). (rupress.org)
  • T cells recognize and respond to processed peptide antigens presented by MHC (human ortholog HLA) molecules through the T cell receptor (TCR) in a highly sensitive and specific manner. (jove.com)
  • Lirilumab attaches to and blocks a group of molecules called Killer Cell Immunoglobulin-Like Receptor (KIR). (cancer.gov)
  • The interaction of HLA molecules expressed on normal cells with HLA class I-specific NK receptors results in protection of these cells from NK-mediated lysis. (aacrjournals.org)
  • On the other hand, NK cells can kill target cells in the absence of interaction between inhibitory receptors and HLA class I molecules. (aacrjournals.org)
  • Changes in these cells post-BMT include cytokine and eicosanoid dysregulations, scavenger receptor alterations, changes in micro RNA profiles, and alterations in intracellular signaling molecules that limit bacterial phagocytosis and killing. (ebscohost.com)
  • Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. (biomedcentral.com)
  • Another distinguishing feature of KIR molecules is the number of extracellular immunoglobulin (Ig) domains, numbered D0, D1 and D2. (biomedcentral.com)
  • This mini-review provides an overview of the mechanisms of action of major immune checkpoint molecules as well as highlights checkpoint inhibitor antibodies in clinical development. (bio-rad-antibodies.com)
  • KIR molecules are expressed on natural killer (NK) cells, which are central to the anti-viral/anti-tumor innate immune response, as well as certain T cell subsets. (cancer.gov)
  • KIR molecules are expressed on natural killer (NK) cells, critical components of the innate immune system that are directly involved in the anti-viral/anti-tumor immune response. (ragoninstitute.org)
  • Upon binding of HLA ligand, KIR molecules regulate cytotoxicity and cytokine production through balanced control of activation and inhibition of NK cells. (ragoninstitute.org)
  • KIR are expressed on a subset of T cells as well, affirming their role in both innate and adaptive immunity, but they are distinct from other NK cell receptors in that they are exceptionally diverse and rapidly evolving (characteristics they share with the HLA molecules). (ragoninstitute.org)
  • We provide evidence, in the amphibian Xenopus laevis, consistent with an evolutionarily conserved and crucial role of the immune system in controlling neoplasia, which involves a striking variety of anti-tumoral immune effectors including conventional CTLs, c lassical MHC c lass Ia u nrestricted CTLs (CCU-CTLs) that interact with nonclassical MHC class Ib molecules, CD8 NKT-like cells and NK cells. (pubmedcentralcanada.ca)
  • HLA likewise forms an integral part of the innate immune response through the binding of killer- cell immunoglobulin-like receptor (KIR) molecules, which regulate the response of natural killer (NK) cel s. (who.int)
  • The peptide-binding groove binds killer-cell immunoglobulin-like receptor exons, while the polymorphisms reside endogenously derived peptides, which in (KIR) molecules on the surfaces of natural in gene regions that encode the peptide- turn are recognised by the TCR on CD8+ killer (NK) cel s and the recognition and binding groove. (who.int)
  • Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. (sciencemag.org)
  • These molecules bind and present processed peptide to circulating T-cell lymphocytes and are crucial to both cellular and humoral immune responses. (chori.org)
  • NK cells are effector cells of the innate immune system that recognize the absence of HLA class I molecules from the surface of virally infected cells and target these cells for destruction through cytotoxicity and pro-inflammatory cytokine production1 (Figure 2). (chori.org)
  • Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. (nature.com)
  • These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC. (nature.com)
  • Combination of uterine natural killer cell immunoglobulin receptor haplotype and trophoblastic HLA-C ligand influences the risk of pregnancy loss: a retrospective cohort analysis of direct embryo genotyping data from euploid transfers. (harvard.edu)
  • Therapeutic strategies targeting regulation of NK cell receptor and ligand system have shown great promise for treatment of cancer and viral infectious diseases. (els.net)
  • This implied the existence of other receptor/ligand interactions that trigger NK cell-mediated target cell lysis. (jimmunol.org)
  • The ligand-receptor interaction is dominated by charge complementarity with HLA-C specificity being determined by the residue at position 44, as was first shown in binding experiments ( 19 ). (rupress.org)
  • [2] In this sense, a receptor is a protein-molecule that recognizes and responds to endogenous chemical signals, e.g. an acetylcholine receptor recognizes and responds to its endogenous ligand , acetylcholine . (wikipedia.org)
  • [1] A molecule that binds to a receptor is called a ligand , and can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter , hormone , pharmaceutical drug, toxin, or parts of the outside of a virus or microbe. (wikipedia.org)
  • The endogenously designated -molecule for a particular receptor is referred to as its endogenous ligand. (wikipedia.org)
  • E.g. the endogenous ligand for the nicotinic acetylcholine receptor is acetylcholine but the receptor can also be activated by nicotine and blocked by curare . (wikipedia.org)
  • When a ligand binds to its corresponding receptor, it activates or inhibits the receptor's associated biochemical pathway. (wikipedia.org)
  • Type 3: Kinase-linked and related receptors (see " Receptor tyrosine kinase ", and " Enzyme-linked receptor ") - They are composed of an extracellular domain containing the ligand binding site and an intracellular domain, often with enzymatic-function, linked by a single transmembrane alpha helix. (wikipedia.org)
  • KIR proteins with long tailed cytoplasmic domains transduce the inhibitory signals upon the ligand binding via an immune tyrosine-based inhibitory motif (ITIM), whereas the KIR proteins of short-tailed cytoplasmic domain lack the ITIM and instead associate with Tyrosine kinase binding protein (TYRO) to transduce activating signals. (wikipedia.org)
  • The protein KIR2DL3 transduces inhibitory signals upon the ligand binding via an immune tyrosine-based inhibitory motif (ITIM) to its long inner cytoplasmic tail. (wikipedia.org)
  • In the present study, we assessed the susceptibility of freshly isolated neuroblastoma cells to killing mediated by normal human natural killer (NK) cells and analyzed the receptor-ligand interactions that regulate this event. (aacrjournals.org)
  • Remarkably, susceptibility to lysis directly correlated with the surface expression, on neuroblasts, of poliovirus receptor [PVR (CD155)], a ligand for the DNAX accessory molecule-1 [DNAM-1 (CD226)] triggering receptor expressed by NK cells. (aacrjournals.org)
  • Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR) and HLA class I ligand interactions. (jove.com)
  • Inhibitory KIR recognition of cognate HLA class I ligand is responsible for NK cell education, which makes them tolerant of healthy cells, but responsive to unhealthy cells having reduced expression of HLA class I. KIR A and KIR B are functionally distinctive KIR haplotype groups that differ in KIR gene content. (bloodjournal.org)
  • We have detected novel associations between specific KIR/HLA genotypes that are known to behave as receptor-ligand pairs and disease outcomes to infection (HIV and hepatitis C virus [HCV]), cancer (nasopharyngeal carcinoma [NPC] and cervical neoplasia), autoimmune disease (psoriatic arthritis), inflammatory disease (Crohn's and ulcerative colitis), and maternal-fetal disease (pre-eclampsia, miscarriage, and fetal growth restriction). (ragoninstitute.org)
  • Tormo, J., Natarajan, K., Margulies, D. H. and Mariuzza, R. A., Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. (wiley.com)
  • Tumor cells can exploit these pathways and ultimately elude immunosurveillance by activating these checkpoint receptors via ligand over-expression resulting in T-cell exhaustion. (onclive.com)
  • Within the IBD2 loci lies the lectin-like natural killer (NK) receptor gene NKG2D ( KLRK1 ) located at 12p13.2-p12.3. (nature.com)
  • The killer immunoglobulin-like receptor ( KIR ) gene family is located within the IBD6 linkage region at chromosome 19q13.4. (nature.com)
  • However, although many different gene combinations have been found in the human Caucasian population, the studies described in this thesis show that there is a limited amount of patterns that define the KIR locus. (uva.nl)
  • In conclusion, the work in this thesis is centered on mapping KIR gene expression variation, to better understand its role in human disease. (uva.nl)
  • Bashirova AA, Martin MP, McVicar DW, Carrington M (2006) The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense. (springer.com)
  • As both KIR and MHC class I are diverse and evolve rapidly, their functional binding relationships must be constantly challenged, through independent segregation of the two gene families in populations and by the production of new variants through recombination and mutation. (rupress.org)
  • In vitro -stimulated NK cells from healthy donors and pediatric leukemia patients were gene modified with CD19 or G D2 -specific chimeric receptors containing either the T-cell receptor ζ or 2B4 endodomain alone or combined. (aacrjournals.org)
  • Requires the MHC , T-cell receptors ( TCR ) and immunoglobulins (Ig) as well as enzymes with a recombinase activity (for the rearrangements at TCR and Ig gene loci). (tripod.com)
  • Cattle have undergone significant gene expansion within two of the major NK receptor encoding complexes, the leukocyte receptor complex (LRC) and natural killer complex (NKC). (gla.ac.uk)
  • Since few KIR remain orthologous between species, with only one of them, KIR2DL4 , shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. (biomedcentral.com)
  • One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. (biomedcentral.com)
  • the CMV receptor gene, US28 (Pleskoff et al. (clinicaltrials.gov)
  • Activated T cells are primary mediators of immune effector functions and as such, they express multiple co-inhibitory receptors such as lymphocyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). (bio-rad-antibodies.com)
  • A greater understanding of the evolutionary and molecular genetic characteristics of the MHC and KIR gene cluster is also a key objective of my laboratory. (ragoninstitute.org)
  • The Trachtenberg lab has developed multiple sophisticated methods for analyzing HLA and KIR gene complexes, which in humans are found on chromosome 6 and 9, respectively. (chori.org)
  • Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. (prolekare.cz)
  • NK cells do not express variable antigen specific receptors. (frontiersin.org)
  • We highlight cutting-edge immunotherapeutic strategies in preclinical and clinical development such as adoptive NK cell transfer, chimeric antigen receptor-expressing NK cells (CAR-NKs), bispecific and trispecific killer cell engagers (BiKEs and TriKEs), checkpoint blockade, and oncolytic virotherapy. (jci.org)
  • This cooperative research group supports projects defining the association between variations in the human leukocyte antigen (HLA), also known as the Major Histocompatibility Complex (MHC), and natural killer cell immunoglobulin-like receptor (KIR) genetic regions and immune-mediated diseases, including outcomes following cell, tissue, and organ transplantation. (nih.gov)
  • This cooperative research group supports studies to discover and characterize associations between polymorphisms in the human leukocyte antigen (HLA, also known as the Major Histocompatibility Complex or MHC), and natural killer cell immunoglobulin-like receptor (KIR) genomic regions and (1) immune-mediated diseases, including risk and phenotype, and (2) cell, tissue, and organ transplantation outcomes, including rejection, tolerance, or graft versus host disease (GVHD). (nih.gov)
  • An additional innovative approach to direct NK cell activity is genetic reprogramming with chimeric antigen receptors (CAR). (frontiersin.org)
  • In contrast to T and B cells, NK cells do not express rearranged receptors recognizing a single antigen on the target cell. (rupress.org)
  • This uptake is dependent on specific receptors on the effector cells and may lead to functional effects such as fratricide in T cells and increased antigen-presenting capability of B cells ( 10 , 11 ). (rupress.org)
  • Have the ability to lyse target cells without prior sensitization antigen and regulate the immune responses by secreting chemokine adaptive and cytokines. (wikipedia.org)
  • Activation of NK cells is determined by integration of inhibitory signals and activating issued by several families of different receptors, including immunoglobulin-like killer cell receptors (KIR) that predominantly recognize antigens of class I human leukocyte antigen ( HLA). (wikipedia.org)
  • Integration of the 2B4 endodomain into T-cell receptor ζ chimeric receptors significantly enhanced all aspects of the NK cell activation response to antigen-expressing leukemia or neuroblastoma cells, including CD25 up-regulation, secretion of IFN-γ and tumor necrosis factor-α, release of cytolytic granules, and growth inhibition, and overcame NK cell resistance of autologous leukemia cells while maintaining antigen specificity. (aacrjournals.org)
  • Besides antigen-specific CTLs, cellular components of the innate immune system can contribute to immune surveillance of malignant cell growth. (aacrjournals.org)
  • Strategies combining NK cell infusions with CD16-binding antibodies or immune engagers could make NK cells antigen specific. (bloodjournal.org)
  • Extensive genetic polymorphism is a primary characteristic of the human leukocyte antigen (HLA) class I and class II loci within the major histocompatibility complex (MHC), which encode products that present antigenic peptides to T cells, initiating an adaptive immune response and clearance of foreign material. (cancer.gov)
  • The major histocompatibility complex, known as the human leukocyte antigen (HLA) complex in humans, forms an integral component of adaptive T cell immunity by presenting self and non-self peptides to the T cell receptor, thereby allowing clonal expansion of responding peptide-specific CD4+ and CD8+ T cel s. (who.int)
  • We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. (rcsb.org)
  • The present disclosure relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region. (patents.com)
  • Killer immunoglobulin-like receptors (KIRs) are proteins that control how activated part of the immune system can become. (mskcc.org)
  • KIR proteins regulate NK cells. (medindia.net)
  • Activation of these cells depends partly on a set of NK cell-surface proteins called activating killer cell immunoglobulin-like receptors (KIRs). (the-scientist.com)
  • Using human cell lines, the team showed that major histocompatibility complex proteins-important components of the vertebrate immune system-on virus-infected cells present this sequence to KIR2DS2, which then activates NK cells to inhibit viral replication. (the-scientist.com)
  • Despite these differences, both ITAM and the inhibitory receptor tails contain YxxL motifs, which raised the possibility that the cytoplasmic part of inhibitory receptors associates with proteins containing Src homology 2 (SH2) domains. (jimmunol.org)
  • Activating receptors have a short cytoplasmic tail and exert their function via associated adapter proteins bearing immunoreceptor tyrosine-based activation motifs. (jimmunol.org)
  • Receptor proteins can be classified by their location. (wikipedia.org)
  • [3] The aforementioned receptors are coupled to different intracellular effector systems via G proteins . (wikipedia.org)
  • PD-1 and KIR are proteins present mainly on immune system cells, and each controls part of the immune system by shutting it down. (cancer.gov)
  • The subsets of the KIR proteins are classified by their number of extracellular IG domains and by whether they have a long (L) or short (S) cytoplasmic domain-tail. (wikipedia.org)
  • The KIR proteins are thought to play an important role in regulating of the immune responses. (wikipedia.org)
  • These cells have unique proteins on their surface called killer-cell immunoglobulin receptors (KIRs), which recognise proteins called MHC on the invading fetal cells. (cam.ac.uk)
  • Immune suppressive checkpoint proteins have been identified that negatively regulate the immune system, resulting in suppressed T-cell inflammatory responses and prevention of autoimmunity (CTLA-4, PD-1, LAG-3, TIM-3, KIRs). (onclive.com)
  • Immune activating proteins have also been identified (4-1BB, GITR) and represent an additional viable therapeutic target. (onclive.com)
  • Activating KIRs on Educated NK Cells Support Downregulation of CD226 and Inefficient Tumor Immunosurveillance. (nih.gov)
  • NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome. (nih.gov)
  • Dr. Blay states that the overall goal of the research is 'to understand how immune cells, white blood cells, contribute to tumor progression and can be manipulated to eradicate cancer. (sarcomahelp.org)
  • Conversely, KIR recognition of "missing self-HLA" - due to HLA loss or HLA/KIR mismatch - triggers NK-mediated tumor rejection. (frontiersin.org)
  • BCG vaccine may help the body build an effective immune response to kill tumor cells. (cancer.gov)
  • In summary, current models hold that tumor antigens are present and induce immune reactivity during incipient tumor growth and that tumors subsequently develop properties to evade these immune responses. (medscape.com)
  • The challenge to the current field is to elucidate the biology of host-tumor interactions at the time of clinical presentation with cancer and to develop approaches that diminish the capacity for tumors to evade immunity and amplify host antitumor immune responses. (medscape.com)
  • Novel natural killer (NK) cell-directed strategies in cancer immunotherapy aim at specifically modulating the balance between NK cell receptor signals toward tumor-specific activation. (aacrjournals.org)
  • Apoptosis is often induced by activation of death receptors (DR) belonging to the tumor necrosis factor receptor (TNFR) family. (tripod.com)
  • In cancer, immune checkpoint mechanisms are often activated to suppress the nascent anti-tumor immune response. (bio-rad-antibodies.com)
  • these tools will move us considerably further along in the search to understand the role of the immune response in the early development of tumor. (aacrjournals.org)
  • Accumulated evidence indicates that cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. (jcancer.org)
  • Immunosuppression and tumor escape from immune recognition are thought to be major factors responsible for the establishment and progression of cancer, however, neither underlying physiological significance nor the exact mechanisms by which immunosuppression occurs are well understood. (jcancer.org)
  • On the other hand, the cellular immune response includes the activation of CD4 + Th1 cells and CD8 + cytotoxic lymphocytes and the synthesis and release of proinflammatory cytokines such as interleukin-12 (IL-12), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) ( 6 , 21 ). (asm.org)
  • Given its ability to disable the complement cascade and facilitate immune evasion by tumor cells, DAF/CD55 has received attention as a potential therapeutic target for the treatment of human malignancies. (cellsignal.com)
  • Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target not the tumor, but the host immune system, therapies that possess unique adverse event profiles, and therapies that might cure many types of cancer. (biomedcentral.com)
  • Because immune-targeted agents (ITAs) act against tumors by modulating immune cells instead of tumor cells, they do not demonstrate the conventional correlative relationship between toxicity and efficacy. (biomedcentral.com)
  • Therefore, tuning down the expression of inhibitory receptors on NK cells would increase their response to tumor cells. (aacrjournals.org)
  • The emergence of immune checkpoint inhibitors as an effective treatment strategy is a result of increased understanding of the elaborate relationship between tumor cells, their microenvironment and the host immune response. (onclive.com)
  • The coupling of external beam radiation therapy with immune checkpoint inhibition provides an opportunity for synergistic anti-tumor effects. (onclive.com)
  • Through activation of co-stimulatory receptors, or antagonization of inhibitory signals, T-cell responses toward tumor antigens can be enhanced and represent an exciting cancer therapeutic strategy that is transforming the oncology world. (onclive.com)
  • Several investigations demonstrate the capacity for local radiation therapy to engender systemic (abscopal) anti-tumor effects that are immune-mediated. (onclive.com)
  • The local and distant immune responses elicited by radiation therapy can have disparate effects on tumor activity: resulting either in continued tumor growth or tumor cell death. (onclive.com)
  • High-dimensional single cell assays are combined with immune informatics to examine the dynamic shaping of human NK cell repertoires during viral infection, tumor transformation and following stem cell transplantation. (icgeb.org)
  • NK cells play a critical role in immune surveillance and control of tumor growth. (esmo.org)
  • Killer-cell immunoglobulin-like receptors (KIR) are important in regulating NK cell activation and blocking KIR function may be a key strategy potentiating anti-tumor immune response, particularly in combination with other immuno-oncology therapies. (esmo.org)
  • The Killer Immunoglobulin-like Receptors (KIRs) are a family of highly variable receptors which regulate cytotoxicity of Natural Killer (NK) cells and a subset of T-cells. (uva.nl)
  • As a member of the Cancer and Inflammation Program, Dr. McVicar uses a variety of cellular and molecular techniques to understand the biology and biochemistry of a variety of receptor systems including the triggering receptors expressed on myeloid cells (TREM) that regulate neutrophils, macrophages, monocytes, dendritic cells and platelets, and the killer Ig-like receptors (KIR) that regulate natural killer (NK) cells. (cancer.gov)
  • These signals that regulate an immune response are known as immune checkpoints. (bio-rad-antibodies.com)
  • A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. (harvard.edu)
  • KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. (harvard.edu)
  • While the primary function of T cells is to mediate protective immune responses to foreign antigens presented by self-MHC, T cells respond robustly to antigenic differences in allogeneic tissues. (jove.com)
  • Inhibitory receptors [e.g., killer immunoglobulin receptors (KIR)] interact with self-MHC class I antigens and protect normal cells from NK cell attack. (aacrjournals.org)
  • Overt or uncontrolled immune responses to pathogens or mutated/overexpressed self-antigens can cause inflammatory tissue damage and autoimmune diseases. (bio-rad-antibodies.com)
  • Dr. Carrington's group studies the influence of human leukocyte antigens (HLA) and specific KIR/HLA genotypes on risk of and outcomes to infection, cancer, autoimmune disease, and maternal-fetal disease. (cancer.gov)
  • These signaling pathways are designed to allow optimal immune response to foreign antigens but prevent self-harm from an over reacting immune response. (bio-rad-antibodies.com)
  • Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism. (lu.se)
  • The receptor inhibition model became widely accepted following the molecular identification of an NK cell receptor that prevented the lysis of target cells expressing certain MHC class I alleles ( 3 ). (jimmunol.org)
  • Members of the KIR family recognize subsets of HLA-A, -B, or -C alleles and are highly polymorphic ( 1 ). (jimmunol.org)
  • This idea is based on the existence of a NK cell subset expressing a specific inhibitory receptor for allogeneic MHC alleles. (asm.org)
  • In recent years, NK-cells have also been recognized as regulatory cells, which are able to interact with other cells of the immune system, such as dendritic cells (DC), monocytes/macrophages, and T cells, thereby influencing the innate and adaptive immune responses [ 2 - 5 ]. (hindawi.com)
  • NF-kB, An Evolutionarily Conserved Mediator of Immune and Inflammatory Responses. (indigo.ca)
  • Inflammation is one of the first responses of the immune system to infection or irritation. (wikipedia.org)
  • Long EO (1999) Regulation of immune responses through inhibitory receptors. (springer.com)
  • Upon receptor triggering, a structured interface called the immune synapse assembles, which facilitates signal integration and controls NK cell responses. (sciencemag.org)
  • These sarcomas are therefore more likely to be recognized as foreign and consequently to attract immune responses. (sarcomahelp.org)
  • Natural Killer (NK) cells are the immune effector cells that likely mediate these responses. (jax.org)
  • Overcoming this barrier to immune surveillance, multiple approaches to enhance NK-mediated responses are being investigated since two decades. (frontiersin.org)
  • Patients develop spontaneous innate and acquired immune responses to their tumors. (medscape.com)
  • Merchant and colleagues also suggest that T-cell-depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of patients with lymphopenic cancer could prevent metastatic recurrence of solid tumors. (medscape.com)
  • This immunity plays a critical role in initiating adaptive immune responses. (medscape.com)
  • Innate immunity includes the role of toll-like receptors (TLRs) in improving antitumor and vaccine responses, muramyl tripeptide phosphatidylethanolamine (MTP-PE) in osteosarcoma, and natural killer (NK) cell-killer immunoglobulinlike receptor (KIR) mismatch. (medscape.com)
  • Immunogenetic factors are likely to modulate various aspects of physiological cellular immune responses and have been implicated in the pathogenesis of T-cell-mediated autoimmune diseases. (haematologica.org)
  • Furthermore, the currently proposed molecular markers of exaggerated immune response appear ubiquitous among various autoimmune T-cell-mediated syndromes, despite the heterogeneous clinical phenotypes observed, implying the presence of additional factors contributing to pathological clonal responses. (haematologica.org)
  • Natural Killer (NK) cells are important in early innate immune responses to viral infections. (jove.com)
  • The journal's scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. (elsevier.com)
  • Infection with HIV, the virus that causes AIDS, results in substantial CD4 + T cell loss, which impairs immune responses to bacterial and fungal infections. (sciencemag.org)
  • A vital defect in the immune systems of HIV-infected individuals is the loss of CD4 + T cells, resulting in impaired immune responses. (sciencemag.org)
  • We hypothesized that there were CD4 + T cell-dependent and CD4 + T cell-independent alterations in the immune responses of HIV-1 + individuals. (sciencemag.org)
  • I am an Infectious Diseases specialist with a research program in human immunology focused on malaria-specific immune responses in pregnancy and infancy. (stanford.edu)
  • The innate and adaptive immune responses are thought to be important in determining viral outcomes. (bmj.com)
  • In addition, there is substantial evidence which indicates that immune responses are inhibited by oral tumors, and this may largely be responsible for their induction and progression. (jcancer.org)
  • There are three important role in immune responses. (who.int)
  • Emerging studies indicate that inhibitory receptors such as cytotoxic T lymphocyte-associated 4 (CTLA-4), programmed cell death 1 (PD-1), and T-cell Ig and ITIM domain (TIGIT) on T and NK cells can suppress antitumor responses ( 12-16 ). (aacrjournals.org)
  • Immune homeostasis is necessary to mount appropriate destructive immune responses towards threatening pathogens while limiting excessive responses towards host tissues that would result in autoimmunity. (onclive.com)
  • This strategy is also valid among patients with hematologic malignancies where innovative combination therapies to improve responses to immune checkpoint blockade are needed to expand the potential therapeutic benefit of immunotherapy. (onclive.com)
  • The special role of HLA-G in the maternal-fetal interface has been attributed to its ability to interact with specific receptors found on maternal immune cells. (jove.com)
  • They comprise, among others, the killer cell immunoglobulin-like receptors (KIR), killer cell lectin type receptors (KLR), and natural cytotoxic receptors (NCR) as well as immunoglobulin Fc receptors (FcR) and complement receptors [ 8 - 10 ]. (hindawi.com)
  • Binding of KIR to "self" HLA acts as an inhibitory signal, preventing NK cell cytotoxic activity. (jax.org)
  • As expected, KIR + /NKG2A - NK cells were cytotoxic when co-cultured with HLA-mismatched cells, but not when co-cultured with syngeneic targets. (jax.org)
  • This experiment demonstrated that the anti-NKG2A antibody could block NKG2A binding to HLA-E to stimulate the NK cells' cytotoxic activity and that the KIR - /NKG2A + cells had the same level of cytotoxic response as the KIR + /NKG2A - NK cells when the NKG2A inhibitory pathway was blocked. (jax.org)
  • Background Large granular lymphocyte leukemia is a semi-autonomous clonal proliferation of cytotoxic T cells accompanied by immune cytopenias and various autoimmune conditions. (haematologica.org)
  • Background/Aims -Killer inhibitory receptors (KIR) have a modulating effect on the cytotoxic functions of natural killer (NK) cells and T cells. (bmj.com)
  • Because lymphoma cells often have the same receptors as their non-neoplastic counterparts, this study investigated the expression of KIR on well defined groups of NK and T cell lymphomas, with and without a cytotoxic phenotype, from different sites of origin. (bmj.com)
  • Methods -Nine CD56 + /CD3 − NK cell lymphomas, 29 CD3 + /CD56 − T cell lymphomas with a cytotoxic phenotype, and 19 T cell lymphomas without a cytotoxic phenotype were stained for KIR using monoclonal antibodies specific for CD94, CD158a, and CD158b. (bmj.com)
  • Moreover, enteropathy-type T cell lymphomas with a cytotoxic phenotype showed KIR expression (three cases expressing CD94 and one case expressing CD158a). (bmj.com)
  • All nodal and extranodal non-intestinal T cell lymphomas with or without a cytotoxic phenotype lacked expression of KIR. (bmj.com)
  • Conclusions -These results show that KIR expression is restricted to CD56 + /CD3 − true NK cell lymphomas originating from the nose, gut, and skin, as well as in a subset of extranodal T cell lymphomas originating from the small intestine, which possessed a cytotoxic phenotype. (bmj.com)
  • Furthermore, it has been reported that HPV infection is associated with a reduction in the expression of different innate immune receptors, including Toll-like receptor 9 (TLR9) ( 9 ), NKp30, NKp46, and NKG2D, diminishing the cytotoxic activity NK cells ( 2 , 7 ). (asm.org)
  • Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. (biomedcentral.com)
  • In March 2011, the US Food and Drug Administration (FDA) approved ipilimumab, an antibody against cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), and marked the first, approved, immune checkpoint modulator that significantly improved survival in patients with advanced melanoma. (biomedcentral.com)
  • Although they share similar mechanisms of killing with cytotoxic T cells ( 3, 4 ), NK cells recognize targets through families of activating and inhibitory receptors. (aacrjournals.org)
  • Sequence comparisons of the cytoplasmic tails of the newly cloned NK cell receptors with inhibitory function provided the first insight into this issue. (jimmunol.org)
  • In addition to regulating NK cell activation, signals coming from activating and inhibitory receptors also tune the steady-state responsiveness of NK cells to future stimuli, in a process called NK cell education (reviewed in refs. (jci.org)
  • NK cells express numerous activating and inhibitory receptors. (bloodjournal.org)
  • G protein-coupled receptors (metabotropic) - This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e.g. dopamine, metabotropic glutamate. (wikipedia.org)
  • Their activity is controlled through a balance of signals from inhibitory and activating receptors, with one important family of receptors being the killer-cell immunoglobulin-like receptors (KIR). (tcd.ie)
  • Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. (hindawi.com)
  • Referred to as NK receptors, KIR are also expressed on subsets of CD4, CD8, and γδ T cells ( 4 ). (jimmunol.org)
  • Murine NK cells express inhibitory receptors of the Ly49 family, which consists of at least 13 members expressed on overlapping subsets of NK cells. (rupress.org)
  • KIR2DL3, Killer cell immunoglobulin-like receptor 2DL3 is a transmembrane glycoprotein expressed by the natural killer cells and the subsets of the T-cells. (wikipedia.org)
  • Similar analysis of immune cells populations, rather than of purified subsets, may help to identify network-level effects in other diseases. (sciencemag.org)
  • This prevented the transduction of inhibitory signals by KIR and consequently resulted in target cell lysis despite the fact that the inhibitory receptor engaged MHC class I ( 1 ). (jimmunol.org)
  • In humans, dominant inhibitory signals are transduced by Killer Immunoglobulin Like Receptors (KIR) recognizing cognate HLA class I on target cells. (frontiersin.org)
  • To prevent this, the breadth and magnitude of the immune response is regulated by a balance between co-stimulatory and inhibitory signals. (bio-rad-antibodies.com)
  • This is achieved via a highly regulated balance between T-cell co-stimulatory and inhibitory signals, which collectively are known as immune checkpoints. (onclive.com)
  • Important NK activating receptors include NKG2D ( 11 ) and three members of the natural cytotoxicity receptors group (NCR): NKp46 ( 12 ), NKp44 ( 13 ), and NKp30 ( 14 ). (frontiersin.org)
  • Barber A, Meehan KR and Sentman CL (2011) Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor‐expressing T cells. (els.net)
  • Results Our analysis found an association with MICA , a non-peptide-presenting, tightly regulated, stress-induced MHC-like molecule and cognate receptor for NKG2D, found abundantly on large granular lymphocyte leukemia cells. (haematologica.org)
  • TG-driven CIK cells expressed a constellation of NK activating/inhibitory receptors, such as CD158a and CD158b, NKp46, NKG2D and NKG2A/CD94, released high quantities of IL-12p40 and efficiently lysed K562 target cells. (biomedcentral.com)
  • Cancer patient-derived CIK cells were also expanded after priming with TG, but they expressed lower levels of the NKp46 triggering receptor and NKG2D activating receptor, thus manifesting a reduced ability to lyse K562 cells. (biomedcentral.com)
  • Toll-Like Receptors: Linking Innate and Adaptive Immunity. (indigo.ca)
  • The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune system ). (wikipedia.org)
  • Furthermore, the immune system, both adaptive and innate, encompassing mesenchymal-derived cells, has been shown to take part to the leukemic niche. (hindawi.com)
  • The adaptive immune system creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen. (wikiversity.org)
  • In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system . (wikiversity.org)
  • These adaptive NK cells display immune memory and methylation signatures like CD8 T cells. (bloodjournal.org)
  • This novel function of HLA may explain some of the many disease associations with these loci that go beyond their classic roles in the adaptive and innate immune response. (cancer.gov)
  • Conclusions This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response. (bmj.com)
  • Human cytomegalovirus (CMV)-induced adaptive natural killer (NK) cells display distinct phenotypic and functional characteristics, including properties of immune memory. (aacrjournals.org)
  • Here we report that relative to conventional NK cells, adaptive NK cells express lower levels of the inhibitory receptor T-cell Ig and ITIM domain (TIGIT), which results in resistance to immune suppression mediated by myeloid-derived suppressor cells (MDSC), as derived from cytokine induction in normal blood or patients with myelodysplastic syndrome. (aacrjournals.org)
  • We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems. (rcsb.org)
  • Vilches, C. and Parham, P., KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. (wiley.com)
  • But how activating KIRs recognize pathogens is poorly understood. (the-scientist.com)
  • The innate immune system is the first line of defense to recognize a set of a pattern-/damage-associated molecular pattern by using pattern recognition receptors. (wikiversity.org)
  • Innate immune cells express pattern recognition receptor s (PRRs) which recognize components that are conserved among broad groups of microorganisms called as pathogen-associated molecular patterns (PAMPs), [2] or substances released by damaged and dying cells called as damage-associated molecular patterns (DAMPs). (wikiversity.org)
  • LILR and KIR receptors recognize HLA-B27 and may influence immune response in ankylosing spondylitis (AS) development. (cdc.gov)
  • Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. (prolekare.cz)
  • The remaining receptor, Treml-2, has no well-defined cytoplasmic signaling domain. (cancer.gov)
  • It turned out that inhibitory KIRs contain motifs in their cytoplasmic domains that resemble ITAM sequences present in the signaling adaptors of activating Ag receptors (YxxLx 6-8 YxxL, in single-letter amino acid code, with x indicating nonconserved positions). (jimmunol.org)
  • The above hypothesis turned out to be correct and it was found that SH2 domain-containing phosphatase (SHP)-1 (HCP, PTP1C) associates directly with human KIRs, that the interaction is dependent on KIR phosphorylation, and that phosphopeptides corresponding to either one of the two tyrosine residues in the KIR cytoplasmic tail activate SHP-1 in vitro ( 1 ). (jimmunol.org)
  • Additional groups soon reported similar findings, extended them to Ly49 receptors, and identified SHP-2 (PTP1D) as an additional phosphatase associated with the cytoplasmic tail of inhibitory receptors ( 10 - 12 ). (jimmunol.org)
  • Immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic domain of these inhibitory receptors mediate their inhibitory functions. (jimmunol.org)
  • [1] Intracellular receptors are those found inside the cell, and include cytoplasmic receptors and nuclear receptors . (wikipedia.org)
  • Inhibitory KIR have longer cytoplasmic tails in comparison to activating KIR, and typically contain two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) which are responsible for repressing the immunoreactivity of NK cells. (biomedcentral.com)
  • The emergence of primate activating KIRs can be accounted by two processes: the alteration in the length and sequence of the cytoplasmic tail in an ancestral long-tailed KIR to eliminate the ITIMs, accompanied by nucleotide changes in the transmembrane (TM) domain to introduce a charged residue [ 12 ]. (biomedcentral.com)
  • Characteristics that would be expected to be present in the common ancestral primate KIR, such as three Ig domains, a long cytoplasmic tail, and two ITIMs providing an inhibitory function, are all present in the KIR3DL0 lineage. (biomedcentral.com)
  • LRR contain either ITIM- or ITAM-sequences in the cytoplasmic domains and include membrane receptors of the Ig- and C-type lectin superfamily. (keystonesymposia.org)
  • NK cells also express another, non-polymorphic, self-inhibitory receptor called NKG2A that binds HLA-E. HLA-E is widely expressed on both normal and cancerous cells. (jax.org)
  • The main goal of my laboratory is to understand the genetic basis for resistance or susceptibility to disease conferred by polymorphic immune response loci. (cancer.gov)
  • Rodents express the paired immunoglobulin receptor (PIR) family which are related to LILR. (springer.com)
  • In recent years, natural killer (NK) cell strategies for cancer immunotherapy have stimulated increasing interest but their clinical application has largely been restricted to the haploidentical hematopoietic stem cell transplantation setting, where natural killer immunoglobulin receptor mismatches between the donor and recipient are exploited to enhance the graft-antileukemia effect. (aacrjournals.org)
  • Aliquots of cells were harvested weekly to monitor the expression of representative members of the killer-like immunoglobulin receptor (KIR), NK inhibitory receptor, NK activating receptor and NK triggering receptor families. (biomedcentral.com)
  • These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease. (jci.org)
  • Given the expanding role of immunotherapies in the treatment of cancer, interactions between tumour cells and immune cells are the subject of intense research. (nature.com)
  • In this Review, we discuss findings relating to the interactions of CTCs and DTCs with the immune system, in the context of cancer immuno-editing, evasion from immune surveillance, and formation of metastases. (nature.com)
  • and, depending on these interactions, it can modify the binding/activity of the receptor. (wikipedia.org)
  • In this study we elucidate the reason for this phenomenon by comparing the specific contact residues responsible for MHC-KIR interactions. (jove.com)
  • We present here a comparative view of the complex interactions between neoplasia and the host immune system. (pubmedcentralcanada.ca)
  • Some interactions are conserved, such as that between human HLA-E and the CD94:NKG2A receptor [7] , whereas others are highly variable, notably those between HLA-A, B, C and killer cell immunoglobulin-like receptors (KIR) [8] . (prolekare.cz)
  • Pointing to the clinical importance of these interactions, various combinations of HLA and KIR factors associate with the outcome of viral infection, susceptibility to autoimmune disease, relapse of leukemia following therapeutic transplantation, and reproductive success [9] - [11] . (prolekare.cz)
  • Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. (nature.com)
  • In addition to supporting HLA and KIR region association studies, a major goal of this program is the assemblage of high-quality, high-resolution genetic data with accompanying disease state and phenotype information. (nih.gov)
  • Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. (sciencemag.org)
  • A major challenge, however, remains to determine how recently identified genetic associations such as interleukin-23 receptor polymorphisms may influence cellular targets in spondyloarthritis. (biomedcentral.com)
  • Understanding the precise role for immunology in the genesis and modification of chronic diseases will depend upon our ability to assess the interaction between individual genetic composition, epigenetic profiles, and environmental factors as they shape and modulate the immune response. (aacrjournals.org)
  • Developing treatments or vaccines for HIV is challenging because the genetic makeup of the virus is constantly changing in an effort to outwit the human immune system. (elifesciences.org)
  • A deeper understanding of the KIR and HLA genetic determinants of disease may provide insight into immunopathology, more effective patient management and the design of clinical trials for new therapeutic interventions. (chori.org)
  • In biochemistry and pharmacology , a receptor is a protein molecule that receives chemical signals from outside a cell. (wikipedia.org)
  • Molecular support for this hypothesis was obtained when Karlhofer and colleagues identified an inhibitory receptor on NK cells that bound an MHC class I molecule ( 4 ). (rupress.org)
  • By mutating these residues to the equivalent classical MHC residues, the HLA-G molecule regained an ability of interacting with KIR inhibitory receptors found on NK cells derived either from peripheral blood or from the decidua. (jove.com)
  • The signaling lymphocyte activation molecule-related receptor 2B4 (CD244) is an important regulator of NK cell activation. (aacrjournals.org)
  • Thus, a native MHC molecule does not induce an immune reaction except when it is presenting a peptide. (tripod.com)
  • We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. (rcsb.org)
  • These data provide a mechanistic insight into the paratope-epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. (rcsb.org)
  • Double staining for CD56 and CD94 in normal lymphoid tissues revealed that KIR was predominantly expressed by CD56 + NK cells and sporadically on CD8 + T cells. (bmj.com)
  • Given their class I specificity and immunomodulatory effects, KIR and ILTs might play an active role in class I-associated disease. (jimmunol.org)
  • Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. (prolekare.cz)
  • Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells. (harvard.edu)
  • These killer cell inhibitory receptors (KIRs) were initially found on a subset of NK cells but subsequent studies revealed that in addition to NK cells, KIRs can also be detected on a subset of CD8 and, rarely, on CD4 positive lymphocytes. (bmj.com)
  • Wende H, Colonna M, Ziegler A et al (1999) Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4. (springer.com)
  • Subsequent work has characterized a diffuse TREM/TREM-like cluster of receptors that occupies approximately 150 Kbp of murine chromosome 17. (cancer.gov)
  • Dominant in the NK cell transplant literature are killer cell immunoglobulin-like receptors (KIR), encoded on chromosome 19q. (bloodjournal.org)
  • Natural killer- (NK-) cells were originally identified by their natural ability to kill target cells and are known for a long time as effector cells of the innate immune system, with an important role in controlling several types of tumors and infections [ 1 ]. (hindawi.com)
  • Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. (wikipedia.org)
  • Background: DNAX-activating protein 12 (DAP12, TYROBP) is a signaling adaptor for several pathogen receptors expressed by cells of the innate immune system (1). (cellsignal.com)
  • The main receptors in the immune system are pattern recognition receptors (PRRs), Toll-like receptors (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors. (wikipedia.org)
  • 1 UC is a complex polygenic condition, characterized by an inappropriate mucosal immune response within the gut to the commensal bacterial flora, leading to ulceration of the colonic mucosa. (nature.com)
  • Recent studies revealed that complex integration of NK receptor signaling controls cytoskeletal rearrangement and other immune synapse-related events. (frontiersin.org)
  • Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense, and Autoimmunity. (indigo.ca)
  • We studied recognition of the disease-associated HLA-B27 allele by immunomodulatory receptors encoded within the leukocyte receptor complex. (jimmunol.org)
  • The classical role of B27 is to present peptides from intracellular pathogens as a heterotrimeric complex with β2 microglobulin for recognition by the T-cell receptor (TCR) of CD8 T-cells. (springer.com)
  • Membrane receptors may be isolated from cell membranes by complex extraction procedures using solvents , detergents , and/or affinity purification . (wikipedia.org)
  • All NK cells potentially lytic for autologous cells but not expressing self-major histocompatibility complex (MHC)-reactive receptors could be eliminated by a negative selection mechanism during ontogeny. (asm.org)
  • We also encourage further development of novel emerging technologies that will continue to enable prospective assessment of the dynamic and complex role played by the immune system in cancer susceptibility. (aacrjournals.org)
  • Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. (jci.org)
  • An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane, which binds to a substance (for example, a cytokine) and causes a response in the immune system. (wikipedia.org)
  • TIGIT is an inhibitory receptor that binds with high affinity to CD155 and with lower affinity to CD112. (aacrjournals.org)
  • More specifically, we have been studying the signal transduction of regulatory receptors of innate immune cells including monocytes/macrophages, natural killer (NK) cells, and most recently, platelets. (cancer.gov)
  • This includes two families of class I-specific regulatory receptors-the killer cell Ig receptors (KIR) 3 and the Ig-like transcripts (ILT). (jimmunol.org)
  • The goal of this conference is to highlight progress in both molecular and cellular biology for a novel class of Leukocyte Regulatory Receptors (LRR) that are involved in positive and negative regulation of immune cell function. (keystonesymposia.org)
  • Three levels of variation determine the repertoire of KIR expression for any given T or NK cell clone: 1) genomic variations in the presence/absence of different KIR loci, 2) allelic variations within KIR loci, and 3) stochastic expression of individual KIR in a given clone. (jimmunol.org)
  • Adjacent to the KIR are ILT loci (also known as LIR, LILR, and CD85). (jimmunol.org)
  • The HLA and KIR/LILR loci are located on different chromosomes (6p and 19q, respectively), so they segregate independently. (cancer.gov)
  • Alternative recognition of different forms of HLA-B27 by KIR or ILT could influence their immunomodulatory function and may imply a role in inflammatory disease. (jimmunol.org)
  • Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. (springer.com)
  • This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. (rcsb.org)
  • Adoptive cellular immunotherapy aims at restoring tumour-cell recognition by the immune system, leading to effective tumour cell killing. (biomedcentral.com)
  • Two NKp46 extracellular (D1-D2) crystal structures were resolved and showed similarity to the extracellular domains of different leukocyte immunoglobulin-like receptors (LIRs) and KIR receptors ( 23 , 24 ). (frontiersin.org)
  • KIR have either two (KIR2D) or three (KIR3D) extracellular immunoglobulin domains and either short (S) or long (L) intracytoplasmic tails which transduce positive and negative signals, respectively ( 4 - 7 ). (rupress.org)
  • Our data reveal a novel mechanism of peripheral immune regulation by inhibitory immune receptors binding to extracellular matrix collagens. (rupress.org)
  • The role of their interaction with neutrophils in shaping the immune response is also being increasingly documented [ 6 , 7 ]. (hindawi.com)
  • 2009) A Role forcis interaction between the inhibitory Ly49A receptor and MHC class I for natural killer cell education. (els.net)
  • Upregulation of B27 2 in spondyloarthritis and differential interaction of β2m-associated HLA-B27 and B27 2 with immune receptors could be involved in the pathogenesis of B27-associated spondyloarthritis (AS). (springer.com)
  • However this interaction is restricted to a limited number of receptors. (jove.com)
  • Engagement of TIGIT with CD155 competes with the interaction between the activating receptor DNAM-1 and CD155, resulting in decreased NK-cell cytolytic activity and IFNγ production ( 16, 18 ). (aacrjournals.org)
  • Recently, much interest in immunology has focused on posttranscriptional membrane-related events occurring when immune effector cells meet their target cells. (rupress.org)
  • A major hurdle to the successful immunotherapy of cancer is represented by the difficulty in generating clinically relevant numbers of immune effector cells with potent in vivo anti-tumour activity, especially in heavily pre-treated patients. (biomedcentral.com)
  • Ligation of immune receptors by B27 2 promotes the survival of KIR-expressing leukocytes and modulates immune cytokine production. (springer.com)
  • Overall we suggest that HLA-G protein evolved to interact with only some of the NK inhibitory receptors thus allowing a control of inhibition, while permitting appropriate NK cell cytokine and growth factor production necessary for a viable maternal fetal interface. (jove.com)
  • Chimeric 2B4 signaling alone failed to induce interleukin-2 receptor up-regulation and cytokine secretion but triggered a specific degranulation response. (aacrjournals.org)
  • Influence of KIR Diversity on Human Immunity. (indigo.ca)
  • In this review, we present the rationale to study immunity in cancer and highlight newly available tools to further elucidate the epidemiologic factors driving individual variation in the immune response in cancer. (aacrjournals.org)
  • It is defined by poor T-cell effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T- cells. (google.com)
  • In contrast, autoimmunity results from a hyperactive immune system attacking normal tissues as if they were foreign organisms. (wikiversity.org)
  • They play a key role in maintaining immune homeostasis and preventing autoimmunity. (bio-rad-antibodies.com)
  • In order to keep the immune response in check, thereby avoiding chronic inflammation and autoimmunity, several immune signaling pathways are employed that stimulate or inhibit the immune response to maintain homeostasis. (bio-rad-antibodies.com)
  • Current Trachtenberg lab research projects include investigating the role of HLA and KIR in autoimmunity, with a special focus on Inflammatory Bowel Disease (Ulcerative Colitis and Crohn's Disease). (chori.org)
  • 2005) Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. (els.net)
  • During the time when attention was focused on how immune cells could be stimulated and costimulated, a small group of immunologists was preoccupied with the question of whether inhibition was a key feature of the regulation of NK cell function. (jimmunol.org)
  • 1 ) provided crucial new information regarding receptor-mediated inhibition and how such receptors transduce signals that counteract cellular activation. (jimmunol.org)
  • One interpretation of these findings was that MHC class I expressed on target cells inhibits NK cells (receptor inhibition). (jimmunol.org)
  • According to the receptor inhibition model, lysis occurs when inhibitory receptors fail to interact with MHC class I on target cells. (jimmunol.org)
  • This approach has been explored initially among patients with solid tumors, however, as investigations into immune checkpoint inhibition have skyrocketed among all malignancies, the potential combinatory role of radiation therapy with immune checkpoint inhibition among patients with hematologic malignancies remains undefined. (onclive.com)
  • Clonal expansion of individual cells, inter-allelic variation and variegated KIR expression levels all contribute to the complexity of KIR expression in humans. (uva.nl)
  • The association of immune population in peripheral blood with a local endometrium condition is the main diagnostic problem in reproductive immunology that is still a matter of debate. (termedia.pl)