Complementarity Determining Regions: Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Base Pairing: Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.RNA, Small Nuclear: Short chains of RNA (100-300 nucleotides long) that are abundant in the nucleus and usually complexed with proteins in snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR). Many function in the processing of messenger RNA precursors. Others, the snoRNAs (RNA, SMALL NUCLEOLAR), are involved with the processing of ribosomal RNA precursors.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).RNA, Ribosomal, 18S: Constituent of the 40S subunit of eukaryotic ribosomes. 18S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.MicroRNAs: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Static Electricity: The accumulation of an electric charge on a objectImmunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Protein Binding: 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.3' Untranslated Regions: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.RNA, Ribosomal, 28S: Constituent of the 60S subunit of eukaryotic ribosomes. 28S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.RNA, Antisense: RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.5' Untranslated Regions: The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Mutation: 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.RNA, Messenger: 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.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.Genes, Immunoglobulin: Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Argonaute Proteins: A family of RNA-binding proteins that has specificity for MICRORNAS and SMALL INTERFERING RNA molecules. The proteins take part in RNA processing events as core components of RNA-induced silencing complex.Biodiversity: The variety of all native living organisms and their various forms and interrelationships.RNA, Complementary: Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)Protein Structure, Tertiary: 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.Gene Rearrangement, B-Lymphocyte, Heavy Chain: Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Antibodies, Catalytic: Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.Antibody Diversity: The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)RNA, Plant: Ribonucleic acid in plants having regulatory and catalytic roles as well as involvement in protein synthesis.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.RNA Precursors: RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.Ligands: 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)Ecosystem: A functional system which includes the organisms of a natural community together with their environment. (McGraw Hill Dictionary of Scientific and Technical Terms, 4th ed)Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.RNA, Ribosomal: The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. (Dorland, 28th ed)RNA, Bacterial: Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Chironomidae: A family of nonbiting midges, in the order DIPTERA. Salivary glands of the genus Chironomus are used in studies of cellular genetics and biochemistry.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Gastropoda: A class in the phylum MOLLUSCA comprised of SNAILS and slugs. The former have coiled external shells and the latter usually lack shells.Comamonas testosteroni: A species of gram-negative, aerobic rods formerly called Pseudomonas testosteroni. It is differentiated from other Comamonas species by its ability to assimilate testosterone and to utilize phenylacetate or maleate as carbon sources.Anticodon: The sequential set of three nucleotides in TRANSFER RNA that interacts with its complement in MESSENGER RNA, the CODON, during translation in the ribosome.RNA, Transfer, Lys: A transfer RNA which is specific for carrying lysine to sites on the ribosomes in preparation for protein synthesis.Templates, Genetic: Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Plants: Multicellular, eukaryotic life forms of kingdom Plantae (sensu lato), comprising the VIRIDIPLANTAE; RHODOPHYTA; and GLAUCOPHYTA; all of which acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations.Epitopes: Sites on an antigen that interact with specific antibodies.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Genetic Code: The meaning ascribed to the BASE SEQUENCE with respect to how it is translated into AMINO ACID SEQUENCE. The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (CODON).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Polychaeta: A class of marine annelids including sandworms, tube worms, clamworms, and fire worms. It includes also the genus Myxicola infundibulum.Sequence Analysis, RNA: A multistage process that includes cloning, physical mapping, subcloning, sequencing, and information analysis of an RNA SEQUENCE.Ribosomes: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Immunoglobulin Joining Region: A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Kinetics: The rate dynamics in chemical or physical systems.RNA Splice Sites: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.RNA, Small Nucleolar: Small nuclear RNAs that are involved in the processing of pre-ribosomal RNA in the nucleolus. Box C/D containing snoRNAs (U14, U15, U16, U20, U21 and U24-U63) direct site-specific methylation of various ribose moieties. Box H/ACA containing snoRNAs (E2, E3, U19, U23, and U64-U72) direct the conversion of specific uridines to pseudouridine. Site-specific cleavages resulting in the mature ribosomal RNAs are directed by snoRNAs U3, U8, U14, U22 and the snoRNA components of RNase MRP and RNase P.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.RNA, Small Untranslated: Short RNA, about 200 base pairs in length or shorter, that does not code for protein.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.Molecular Mimicry: The structure of one molecule that imitates or simulates the structure of a different molecule.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Ribonuclease III: An endoribonuclease that is specific for double-stranded RNA. It plays a role in POST-TRANSCRIPTIONAL RNA PROCESSING of pre-RIBOSOMAL RNA and a variety of other RNA structures that contain double-stranded regions.Codon, Initiator: A codon that directs initiation of protein translation (TRANSLATION, GENETIC) by stimulating the binding of initiator tRNA (RNA, TRANSFER, MET). In prokaryotes, the codons AUG or GUG can act as initiators while in eukaryotes, AUG is the only initiator codon.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).RNA Caps: Nucleic acid structures found on the 5' end of eukaryotic cellular and viral messenger RNA and some heterogeneous nuclear RNAs. These structures, which are positively charged, protect the above specified RNAs at their termini against attack by phosphatases and other nucleases and promote mRNA function at the level of initiation of translation. Analogs of the RNA caps (RNA CAP ANALOGS), which lack the positive charge, inhibit the initiation of protein synthesis.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).RNA-Induced Silencing Complex: A multicomponent, ribonucleoprotein complex comprised of one of the family of ARGONAUTE PROTEINS and the "guide strand" of the one of the 20- to 30-nucleotide small RNAs. RISC cleaves specific RNAs, which are targeted for degradation by homology to these small RNAs. Functions in regulating gene expression are determined by the specific argonaute protein and small RNA including siRNA (RNA, SMALL INTERFERING), miRNA (MICRORNA), or piRNA (PIWI-INTERACTING RNA).Software: Sequential operating programs and data which instruct the functioning of a digital computer.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.RNA, Guide: Small kinetoplastid mitochondrial RNA that plays a major role in RNA EDITING. These molecules form perfect hybrids with edited mRNA sequences and possess nucleotide sequences at their 5'-ends that are complementary to the sequences of the mRNA's immediately downstream of the pre-edited regions.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.RNA Stability: The extent to which an RNA molecule retains its structural integrity and resists degradation by RNASE, and base-catalyzed HYDROLYSIS, under changing in vivo or in vitro conditions.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)RNA Processing, Post-Transcriptional: Post-transcriptional biological modification of messenger, transfer, or ribosomal RNAs or their precursors. It includes cleavage, methylation, thiolation, isopentenylation, pseudouridine formation, conformational changes, and association with ribosomal protein.Receptors, Antigen, T-Cell: 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.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.Myeloma Proteins: Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.Conservation of Natural Resources: The protection, preservation, restoration, and rational use of all resources in the total environment.Cell Nucleolus: Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed)DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.RNA, Fungal: Ribonucleic acid in fungi having regulatory and catalytic roles as well as involvement in protein synthesis.Ribonuclease H: A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.Nucleic Acid Denaturation: Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.Hydrophobic and Hydrophilic Interactions: The thermodynamic interaction between a substance and WATER.Base Composition: The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.RNA, Double-Stranded: RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Endoribonucleases: A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Ribonucleoproteins, Small Nuclear: Highly conserved nuclear RNA-protein complexes that function in RNA processing in the nucleus, including pre-mRNA splicing and pre-mRNA 3'-end processing in the nucleoplasm, and pre-rRNA processing in the nucleolus (see RIBONUCLEOPROTEINS, SMALL NUCLEOLAR).RNA, Untranslated: RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Plankton: Community of tiny aquatic PLANTS and ANIMALS, and photosynthetic BACTERIA, that are either free-floating or suspended in the water, with little or no power of locomotion. They are divided into PHYTOPLANKTON and ZOOPLANKTON.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.DNA, Intergenic: Any of the DNA in between gene-coding DNA, including untranslated regions, 5' and 3' flanking regions, INTRONS, non-functional pseudogenes, and non-functional repetitive sequences. This DNA may or may not encode regulatory functions.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.RNA, Catalytic: RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Antigen-Antibody Complex: 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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Ribonucleoproteins: Complexes of RNA-binding proteins with ribonucleic acids (RNA).Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Surface Properties: Characteristics or attributes of the outer boundaries of objects, including molecules.Peptide Chain Initiation, Translational: A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Bacterial Proteins: Proteins found in any species of bacterium.Crystallization: The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Amino Acid Motifs: 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.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Poaceae: A large family of narrow-leaved herbaceous grasses of the order Cyperales, subclass Commelinidae, class Liliopsida (monocotyledons). Food grains (EDIBLE GRAIN) come from members of this family. RHINITIS, ALLERGIC, SEASONAL can be induced by POLLEN of many of the grasses.Viral Proteins: Proteins found in any species of virus.B-Lymphocytes: 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.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Invertebrates: Animals that have no spinal column.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.RNA, Transfer: The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.Mammals: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.Water: A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Chemistry, Physical: The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Retroelements: Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population.Defective Viruses: Viruses which lack a complete genome so that they cannot completely replicate or cannot form a protein coat. Some are host-dependent defectives, meaning they can replicate only in cell systems which provide the particular genetic function which they lack. Others, called SATELLITE VIRUSES, are able to replicate only when their genetic defect is complemented by a helper virus.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.

Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. (1/723)

To determine whether the antigen-driven T-cell response is involved in the pathogenesis of aplastic anemia (AA), we examined the complementarity-determining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chain (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA patients who did not respond to immunosuppressive therapy and those who obtained unmaintained remission early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In contrast, five patients who needed continuous administration of CyA to maintain remission exhibited a skewed CDR3 size pattern in a number (>40%) of BV subfamilies suggestive of clonal predominance. The skewing of CDR3 size distribution became less pronounced in one of the CyA-dependent patients when the patient achieved unmaintained remission after a 4-year therapy with CyA, whereas it persisted longer than 7 years in the other patient requiring maintenance therapy. Sequencing of BV15 cDNA for which the CDR3 size pattern exhibited apparent clonal predominance in all CyA-dependent patients showed high homology of the amino acid sequence of the CDR3 between two different patients. These findings indicate that antigen-driven expansion of T cells is involved in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis.  (+info)

A peptide derived from a polyreactive monoclonal anti-DNA natural antibody can modulate lupus development in (NZBxNZW)F1 mice. (2/723)

In lupus-prone (NZBxNZW)F1 (B/W) mice, elevated levels of polyreactive autoantibodies bearing the D23 idiotype (Id), characteristic of natural antibodies, were detected before and after the appearance of pathological anti-DNA antibodies. While these D23 Id+ antibodies were able to regulate anti-DNA antibodies in the early stage of the disease, we found that during disease evolution they had lost their normal ability to regulate anti-DNA antibodies and furthermore could participate in the lupus-like syndrome. To explore further the role of the D23 Id+ antibodies, we injected young B/W mice with a peptide corresponding to the VH CDR3 region of the D23 monoclonal natural antibody (mNAb). High levels of monospecific antipeptide, as well as polyreactive antibodies, were induced. Among them, the most markedly enhanced antibody population was DNA-reactive immunoglobulin G1 (IgG1). Compared with controls, these immunized mice had a delayed 50% survival rate and proteinuria developed later. Furthermore, IgG1 able to react with IgG2a anti-DNA monoclonal antibodies derived from B/W mice were also produced after peptide immunization. Thus, a peptide corresponding to the CDR3 of the D23 mNAb antibody might play a role in the regulation of murine lupus.  (+info)

Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease. (3/723)

We examined T-cell receptor (TCR) usage, cytokine production and antibody responses to superantigens in patients with Kawasaki disease (KD) to facilitate a better understanding of the immunopathogenesis of KD. The mean percentage of VB2- or VB6. 5-bearing T cells in peripheral blood mononuclear cells (PBMC) of patients with acute-phase KD was significantly higher than that of patients in the convalescent phase of KD or in healthy donors. Expansion of VB2- or VB6.5-bearing T cells was polyclonal because DNA sequences in the complementarity determining region 3 of VB2- and VB6.5-positive cDNA clones were all different from each other. The plasma levels of interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) were elevated in the acute phase of KD. We previously reported that streptococcal pyrogenic exotoxin C (SPEC) was a potent stimulator of VB2- and VB6.5-positive T cells and, furthermore, serum levels of anti-SPEC antibodies were significantly higher in patients with acute and convalescent KD than in age-matched controls. The results of the present study, together with those of our previous report, suggest that SPEC induces activation and polyclonal expansion of VB2- and VB6.5-positive T cells, and that SPEC-induced activation of T cells may lead to the pathogenesis of KD.  (+info)

Evolution of antigen-specific T cell receptors in vivo: preimmune and antigen-driven selection of preferred complementarity-determining region 3 (CDR3) motifs. (4/723)

Antigen (Ag)-driven selection of helper T cells (Th) in normal animals has been difficult to study and remains poorly understood. Using the major histocompatibility complex class II- restricted murine response to pigeon cytochrome c (PCC), we provide evidence for both preimmune and Ag-driven selection in the evolution of Ag-specific immunity in vivo. Before antigenic challenge, most Valpha11(+)Vbeta3(+) Th (70%) express a critical complementarity-determining region 3 (CDR3) residue (glutamic acid at TCR-alpha93) associated with PCC peptide contact. Over the first 5 d of the primary response, PCC-responsive Valpha11(+)Vbeta3(+) Th expressing eight preferred CDR3 features are rapidly selected in vivo. Clonal dominance is further propagated through selective expansion of the PCC-specific cells with T cell receptor (TCR) of the "best fit." Ag-driven selection is complete before significant emergence of the germinal center reaction. These data argue that thymic selection shapes TCR-alpha V region bias in the preimmune repertoire; however, Ag itself and the nongerminal center microenvironment drive the selective expansion of clones with preferred TCR that dominate the response to Ag in vivo.  (+info)

Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection. (5/723)

Low grade B-cell lymphomas comprise several well defined, clinically and immunophenotypically distinct disease entities. Composite lymphomas showing phenotypic characteristics of more than one of these tumor subtypes in the same site are rare, and both common and separate clonal origins of the two tumor parts have been reported for cases studied by molecular methods. We describe the detailed immunohistochemical and molecular findings in three cases with features of composite low grade B-cell non-Hodgkin's lymphoma (B-NHL). All three neoplasms contained morphologically distinct but interwoven compartments of different cell types, which exhibited discordant expression of several markers, including CD5, CD10, CD43, and cyclin D1. According to their morphology and phenotypes, they were classified as mantle cell lymphoma and follicular lymphoma (Case 1), follicular lymphoma and small lymphocytic lymphoma (Case 2), and mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (Case 3). PCR analysis of DNA obtained from whole tissue sections failed to reveal evidence for biclonality in any of the cases. We therefore isolated cell populations with different antigen expression patterns by laser capture microdissection and analyzed them by polymerase chain reaction amplification and sequencing of clonal immunoglobulin heavy chain gene rearrangements and oncogene rearrangements. Sequence analysis revealed unrelated clonal rearrangements in each of the two tumor parts in all three cases, suggesting distinct clonal origins. In addition, Case 1 showed a bcl-2 rearrangement present only in the follicular lymphoma part. Our findings suggest that low grade B-NHL with two distinct morphological and immunophenotypic patterns in the same anatomical site are frequently biclonal. This is in keeping with current classification schemes, which recognize subtypes of low grade B-NHL as separate disease entities. Furthermore, our analysis demonstrates the power of laser capture microdissection in revealing molecular microheterogeneity in complex neoplasms.  (+info)

Astrocytoma infiltrating lymphocytes include major T cell clonal expansions confined to the CD8 subset. (6/723)

Anaplastic astrocytoma and glioblastoma are frequent and malignant brain tumors that are infiltrated by T lymphocytes. Whether these cells result from non-specific inflammation following blood-brain barrier disruption or an antigen-driven specific immune response is unknown. In this study, an in-depth characterization of TCR diversity in tumor and blood RNA biopsies was performed in a series of 16 patients with malignant astrocytoma. Whilst there was no obvious restriction of the AV and BV gene segment usage, complementarity-determining region 3 size analysis and sequencing of amplified TCR transcripts revealed multiple T cell oligoclonal expansions in all astrocytomas analyzed. Unique T cell clones were present in different adjacent areas of a given tumor, but never detected in the blood. Quantification of the number of TCR clonal transcripts per microg of tumor RNA indicated that certain T cell clonal expansions may represent at least 300 cells/10(6) tumor cells. Furthermore, we demonstrated that the in vivo expanded clones were almost exclusively confined to the CD8(+) subset. Overall, these data suggest that spontaneous antigen-driven immune responses may be elicited against human astrocytoma despite the immunosuppressive microenvironment generated by the brain and the tumor itself. However, the ultimate failure of the immune system to control tumor growth could be the consequence of a deficient CD4 T(h) component of the response. This observation could have important consequences for the development of immunotherapies for astrocytoma patients.  (+info)

Characterisation of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis. (7/723)

OBJECTIVE: To investigate whether identical T cell clonotypes accumulate in multiple rheumatoid joints, the clonality of T cells that had infiltrated into synovial tissue (ST) samples simultaneously obtained from multiple joints of patients with rheumatoid arthritis (RA) was analysed. METHODS: T cell receptor (TCR) beta gene transcripts, amplified by reverse transcription-polymerase chain reaction from ST and peripheral blood lymphocytes of five RA patients, were subjected to single strand conformation polymorphism analysis and DNA sequencing. RESULTS: Approximately 40% of accumulated T cell clonotypes found in one joint of a patient were found in multiple joints in the same patient. Furthermore, identical amino acid sequences were found in TCR beta junctional regions of these clonotypes from different patients with at least one HLA molecule match. CONCLUSIONS: The T cell clonotypes accumulating in multiple rheumatoid joints may be involved in the perpetuation of polyarthritis by reacting to antigens common to these multiple joints.  (+info)

Selection at multiple checkpoints focuses V(H)12 B cell differentiation toward a single B-1 cell specificity. (8/723)

Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express V(H)12 and Vkappa4/5H and are restricted in V(H)CDR3. We have previously reported that anti-PtC V(H)CDR3 is enriched among V(H)12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vkappa4/5H expression among V(H)12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of V(H)12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vkappa4/5H-expressing cells. Thus, the bias for Vkappa4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC V(H)CDR3 and L chain in a high frequency of V(H)12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.  (+info)

*Complementarity-determining region

Complementarity-determining regions (CDRs) are part of the variable chains in immunoglobulins (antibodies) and T cell receptors ... Complementarity determining regions at the US National Library of Medicine Medical Subject Headings (MeSH). ... Framework region Hypervariable region Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology (5th ed.). Saunders, ... these regions are sometimes referred to as hypervariable regions. Within the variable domain, CDR1 and CDR2 are found in the ...

*Somatic hypermutation

These regions correspond to the complementarity determining regions; the sites involved in antigen recognition on the ... The TSM process implies an "in-frame DNA reader" whereby DNA and RNA deaminases at transcribed regions are guided in their ... During B cell division the immunoglobulin variable region DNA is transcribed and translated. The introduction of mutations in ... Somatic hypermutation involves a programmed process of mutation affecting the variable regions of immunoglobulin genes. Unlike ...

*Antigen

... each have distinctly formed complementarity determining regions. Allergen - A substance capable of causing an allergic reaction ... The antibody is said to "match" the antigen in the sense that it can bind to it due to an adaptation performed to a region of ... At the molecular level, an antigen can be characterized by its ability to bind to an antibody's variable Fab region. Different ...

*Antibody

These loops are referred to as the complementarity determining regions (CDRs). The structures of these CDRs have been clustered ... Each heavy chain has two regions, the constant region and the variable region. The constant region is identical in all ... the Fab region of the antibody determines antigen specificity while the Fc region of the antibody determines the antibody's ... or complementarity determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved ...

*Cancer immunotherapy

Humanized antibodies are almost completely human; only the complementarity determining regions of the variable regions are ... Anti-PD-1 drugs contain not only an Fab region that binds PD-1 but also an Fc region. Experimental work indicates that the Fc ... Antibodies are formed of a binding region (Fab) and the Fc region that can be detected by immune system cells via their Fc ... Fc regions are varied: they exist in numerous subtypes and can be further modified, for example with the addition of sugars in ...

*Michael Neuberger

Jones, P. T.; Dear, P. H.; Foote, J.; Neuberger, M. S.; Winter, G. (1986). "Replacing the complementarity-determining regions ...

*1986 in science

"Replacing the complementarity-determining regions in a human antibody with those from a mouse" (PDF). Nature. 321 (6069): 522- ...

*Humanized antibody

... despite the non-human origin of some of its complementarity determining region (CDR) segments responsible for the ability of ... "Humanization of an anti-CD34 monoclonal antibody by complementarity-determining region grafting based on computer-assisted ... The DNA sequence corresponding to the antibody CDRs can then be determined. Once the precise sequence of the desired CDRs are ... by substituting the mouse Fc region of the antibody with that from human) simple chimeras of this type are not usually referred ...

*MRNA display

However, they have demonstrated that two of the five consensus mutations were within the complementarity determining regions ( ... The T7 promoter region allows large-scale in vitro T7 transcription to transcribe the DNA library into an mRNA library, which ... The ribosomal binding site in the 5'-untranslated region (5' UTR) is designed according to the in vitro translation system to ...

*2F5 antibody

... between Antibody 2F5 Neutralization of HIV-1 and Hydrophobicity of Its Heavy Chain Third Complementarity-Determining Region". ... The region DKW of the core epitope must be in a β-turn conformation and have the correct side-chain positions for 2F5 to bind ... 2F5 recognizes an epitope in the membrane-proximal external region (MPER) of HIV-1 gp41. 2F5 then binds to this epitope and its ... 2F5 binds to the variable regions of env and neutralizes the virus before it infects target cells. 2F5 recognizes a core ...

*Polymeric immunoglobulin receptor

Evidence for the involvement of multiple complementarity determining region (CDR)-like loops in receptor domain I". The Journal ... "Genetic mapping of the human polymeric immunoglobulin receptor gene to chromosome region 1q31----q41". Cytogenetics and Cell ... importance of the CDR2-containing region for IgM interaction". Journal of Immunology. 162 (10): 6046-52. PMID 10229845. ...

*T-cell receptor

The variable domain of both the TCR α-chain and β-chain each have three hypervariable or complementarity determining regions ( ... The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while ... Each chain is composed of two extracellular domains: Variable (V) region and a Constant (C) region, both of Immunoglobulin ... The residues in these variable domains are located in two regions of the TCR, at the interface of the α- and β-chains and in ...

*CDR2

... can refer to Complementarity determining region 2 on antibodies Cerebellar degeneration-related protein 2, a protein ...

*Paratope

Each arm of the Y shape of an antibody monomer is tipped with a paratope, which is a set of complementarity determining regions ... It is a small region (of 5 to 10 amino acids[citation needed]) of the antibody's Fv region, part of the fragment antigen- ... The engraved inner portions of idiotype (encircled region no.5 in the above diagram) is the paratope where the epitope of the ... binding (Fab region), and contains parts of the antibody's heavy and light chains. ...

*Idiotype

The variable region of antigen receptors of T cells (TCRs) and B cells (immunoglobulins) contain complementarity determining ... They define the surface and properties of the variable region, determining the antigen specificity and therefore the idiotope ... He also defined the "paratope" to be that part of an antibody variable region that binds to an antigen. The best developed ... Antibody idiotype is determined by: Gene rearrangement Junctional diversity P-nucleotides (palindromic nucleotides at sites of ...

*Theralizumab

The complementarity determining regions of 5.11A1 were cloned into the framework of human IgG and combined with IgG1 (TGN1112) ... The molecule was genetically engineered by transfer of the complementarity determining regions (CDRs) from heavy and light ... Humanised variable regions were subsequently recombined with a human gene coding for the IgG4 gamma chain and with a human gene ... region. According to a report by TeGenero, the F(ab)2 is not able to generate the required stimulation. Unlike the related ...

*Fragment antigen-binding

The variable domain contains the paratope (the antigen-binding site), comprising a set of complementarity determining regions, ... The variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv), which ... The antigen-binding (Fab) fragment is a region on an antibody that binds to antigens. It is composed of one constant and one ... The enzyme pepsin cleaves below the hinge region, so a F(ab')2 fragment and a pFc' fragment is formed. Recently another enzyme ...

*Immunoglobulin superfamily

One end of the Ig domain has a section called the complementarity determining region that is important for the specificity of ... It is believed that the structure of variable subgenes of Ig and the surface immunoglobulin determine the propensity of chronic ...

*Fcα/μR

Yang, Xi; Zhao, Qing; Zhu, Liping; Zhang, Wei (May 2013). "The three complementarity-determining region-like loops in the ...

*Nest (protein structural motif)

... complementarity determining regions) bound to a carboxylate side chain. These have been engineered to give rise to monoclonal ... Their occurrence in cation and anion-binding regions of proteins". Journal of Molecular Biology. 315 (15): 183-191. doi:10.1006 ... successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions ...

*Affilin

... whereas the binding regions of antibodies, called complementarity determining regions, are flexible loops. Historically, ... In both types, the binding region is typically located in a beta sheet structure, ... a process creating regions capable of binding different antigens, depending on which amino acids are exchanged. ...

*Central tolerance

... and gives rise to the complementarity determining regions (CDR). These random combinations and base insertions allow the ... The process of positive selection also determines whether a T cell ultimately becomes a CD4+ cell or a CD8+ cell: prior to ...

*Eculizumab

It is an immunoglobulin G-kappa (IgGκ) consisting of human constant regions and murine complementarity-determining regions ... per person per year price and Pharmac's economic analysis determined the price would need to be halved before the drug was cost ... grafted onto human framework light and heavy chain variable regions. The compound contains two 448-amino acid heavy chains and ...

*Inotuzumab ozogamicin

The antibody, originally called G5/44, was created by grafting the complementarity-determining regions and some framework ...

*Elizabeth Press

... now known as complementarity-determining region 3. Her research also pointed to evidence that at least two genes are involved ... Her studies on antibodies were important in determining the chain structure, and particularly the observation that more than ... Press's work provided the first evidence that immunoglobulin heavy chains had variable regions similar to those observed in ...

*Antiparallel (biochemistry)

The structure of these G-quadruplexes can be determined by a cation. In DNA, the 5' carbon is located at the top of the leading ... Complementarity (molecular biology) Directionality (molecular biology) Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, ... These structures are normally located at the ends of the chromosomes known as the telomeric regions. The G-quadruplex can ...
The target of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (Abs) is the putative trimer of gp120-gp41 heterodimers that decorates the surface of HIV-1 (10, 28, 43, 52, 54). In the case of gp41, it appears that antibody access to neutralizing epitopes may be more restricted than access to those on gp120, since the relevant epitopes on gp41 probably become fully exposed only during HIV-1 envelope-mediated virus-cell membrane fusion (4, 19, 20, 46). The two anti-gp41 monoclonal Abs (MAbs) that are the most potent and broadly neutralizing are the human immunoglobulin G (IgG) MAbs 2F5 and 4E10 (12, 14, 16, 21, 47, 49, 58). The core epitope of 2F5, the most studied of the two MAbs, has been defined conveniently by a short linear sequence, ELDKWA, which is found at the extreme C-terminal end of the C-heptad repeat region on the ectodomain of gp41 (37). MAb 4E10 appears to recognize an epitope immediately C-terminal to the 2F5 epitope. The 4E10 epitope has been defined by the ...
This study investigated whether fingolimod reduced newly produced T and B lymphocytes and T-cell receptor repertoire diversity in peripheral blood in patients
Next-generation sequencing enabled T-cell receptor (TCR) repertoire analysis has gained major attention in scientific as well as clinically driven research. However, despite improvements of sequencing technology, next-generation sequencers produce huge data sets that are usually prone to errors, thus urging the need for improved analysis tools being able to account not only for the large number of sequences but also for sequencing artifacts. TCRProfiler is a tool that includes sequencer generated quality values to improve reliability of TCR repertoire analysis. As a stand alone tool for parallel and detailed analysis, TCRProfiler delimits combinatorial diversity (rearranged germline V, (D), and J genes) and junctional diversity (P(alindromic)-, and N(on-template)-nucleotides) of TCR alpha and/or beta chain sequences. TCRProfiler generates probe-specific statistical repertoire profiles, as well as visualization files to allow fast and comprehensive accession of repertoire diversity. In a single ...
For CDR3 size polymorphism analysis we used the Immunoscope software package. 23 Immunoscope analysis couples fluorescence PCR and software analysis and allows the direct and accurate sizing of a clonal population of T or B cells within a polyclonal milieu. Peripheral blood mononuclear cells (PBMCs) were prepared by centrifugation on single-density gradient (Ficoll Hypaque; Pharmacia, Upsala, Sweden) and processed for Immunoscope analysis, as previously described. 25 An Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cell line (BLCL) was established in the laboratory and maintained as previously described. 26 The vitreous humor was obtained after vitrectomy. Approximately 200 μL of vitreous humor was diluted in a saline solution to a final volume of 1 mL, and the samples were centrifuged immediately (910g for 10 minutes at 4°C). Previous morphologic studies revealed that such amounts of vitreous humor obtained from PIOL patients contain, on average, 1000 cells (Merle-Beral H, ...
Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibodys antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the Complementarity Determining Region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions, and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop
The antigen-binding end of an antibody molecule and green fluorescent protein (GEP) both contain β-strands that are connected by exposed loops. Zeytun et al. have taken advantage of this commonality and engineered libraries of "fluorobodies" by inserting antigen-binding sequences (the complementarity-determining regions) within four of the GFP loops. They isolated fluorobodies that bound specifically to several proteins (ubiquitin, tubulin, and myoglobin) with submicromolar affinities and were used successfully in immunofluorescence microscopy, immunoblots, or flow cytometry. - GJC. NatureBiotechnol. 10.1038/nbt911 (2003).. ...
Surface representation of the CDRs.(A) Surface representation of D7 revealing the gp120 docking interface based on gp120 binding and HIV-1 neutralization result
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The intestinal mucosa is constantly exposed to microbial and dietary antigens, all of which are considered to induce IgA-secreting plasma cells. Thus, the limited IgA repertoire diversity predicted in previous studies (Dunn-Walters et al., 1997, 2000; Holtmeier et al., 2000; Stoel et al., 2005; Yuvaraj et al., 2009) is difficult to reconcile with the broad range of intestinal antigens. In this study, we show that in fact each individual harbors a private polyclonal and highly diverse IgA repertoire. Because we analyzed switched Ig sequences, repertoire analyses performed in this study did not require sorting of plasma cells. Instead, RNA was isolated directly from intestinal tissue, and IgA-encoding transcripts were enriched during reverse transcription. This approach was equivalent to our results obtained when RNA was isolated out of sorted plasma cells. The IgA repertoire showed characteristics reminiscent of the T cell receptor repertoire of CD8+ memory cells (Naumov et al., 2003), i.e., the ...
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B cell antigen receptor (BCR) or antibody diversity arises from somatic recombination of immunoglobulin (Ig) gene segments and is concentrated within the Ig heavy (H) chain complementarity-determining region 3 (CDR-H3). We performed high-throughput sequencing of the expressed antibody heavy chain repertoire from adult torafugu. We found that torafugu use between 70% and 82% of all possible V (variable) D (diversity) J (joining) gene segment combinations and that they share a similar frequency distribution of these VDJ combinations. The CDR-H3 sequence repertoire observed in individuals is biased with the preferential use of a small number of VDJ, dominated by sequences containing inserted nucleotides. We uncovered the common CDR-H3 amino acid (aa) sequences shared by individuals. Common CDR-H3 sequences feature highly convergent nucleic acid recombination compared with private ones. Finally, we observed differences in repertoires between IgM and IgT, including the unequal usage frequencies of V gene
T cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Clonal expansion of T cells correlating with disease activity has been observed in peripheral blood (PB) of SLE subjects. Recently, next-generation sequencing (NGS) of the T cell receptor (TCR) β loci has emerged as a sensitive way to measure the T cell repertoire. In this study, we utilized NGS to assess whether changes in T cell repertoire diversity in PB of SLE patients correlate with or predict changes in disease activity. Total RNA was isolated from the PB of 11 SLE patients. Each subject had three samples, collected at periods of clinical quiescence and at a flare. Twelve age-matched healthy controls (HC) were used for reference. NGS was used to profile the complementarity-determining region 3 (CDR3) of the rearranged TCR β loci. Relative to the HC, SLE patients (at quiescence) demonstrated a 2.2-fold reduction in repertoire diversity in a given PB volume (P |0.0002), a more uneven distribution of the
Downloadable! Empirical research on complementarity between organizational design decisions has traditionally focused on the question of existence of complementarity. In this paper, we take a broader approach to the issue, combining a productivity and an adoption approach, while including a search for contextual variables in the firms strategy that affects complementarity. Analysis of contextual variables is not only interesting per se, but also improves the productivity test for the existence of complementarity. We use our empirical methodology to analyze complementarity between innovation activities: internal research and development (R& D) and external knowledge acquisition. Our results suggest that internal R& D and external knowledge acquisition are complementary innovation activities, but that the degree of complementarity is sensitive to other elements of the firms strategic environment. We identify reliance on basic R& D--the importance of universities and research centers as an
1. The regulation of the immune response: vaccine design, phage-based vaccines, Virus-like-particle vaccines, protein vaccines, Alzheimers Disease immunotherapy, induction of immune responses to self-antigens, correlates of vaccine efficacy, signaling in T cell development and activation, T cell receptor repertoire in Coeliac disease, T cell receptor repertoire of antigen-specific T cell lines ...
functions (append (car display-buffer-overriding-action) , (car user-action) , (car action) , (car display-buffer-default-action))) , (alist (append (cdr display-buffer-overriding-action) , (cdr user-action) , (cdr action) , (cdr display-buffer-default-action)))) , (run-with-args-until-success functions buffer alist))) Elaborating once more on this subject: Let O, U, A and D respectively denote the functions in the cars of display-buffer-overriding-action, user-action, action, and display-buffer-default-action and OL, UL, AL, DL the alists in the corresponding cdrs. Now my original proposal was to run until success (O . (OL UL AL DL)) (U . (UL AL DL)) (A . (AL DL)) (D . (DL)) that is, try the overriding function with all alists, if that fails try the user function with all alists but the overriding one and so on. People raised concerns about misinterpreting the alist concept and Chong proposed to do something like (O . (OL)) (U . (UL)) (A . (AL)) (D . (DL)) instead. I raised concerns about ...
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Use the search fields below to explore our most up to date test repertoire and find user details such as how to order and interpret results. ...
Material and methods Three DMARD-naïve ERA patients (disease duration , 1 year) and three ESRA patients (disease duration ,2 years) were included. All fulfilled the American College of Rheumatology1987 criteria for RA. mRNA was isolated from paired ST and PB samples. A linear amplification with primers for all V(ariable)-genes of the T cell receptor β-chain was performed. The amplified products contain the CDR3s of all T cells. Samples were processed using a Genome Sequencer (454) analysing up to 15 000 receptors per sample, The frequency of each clone was determined by its CDR3 frequency (% of all CDR3s analysed). Clones with a CDR3 frequency of ,1% were arbitrarily considered as highly expanded clones (HECs).. ...
In this report, we describe the molecular and functional characterization of T-cell clones identified in peripheral blood from patients with relapsed myeloma responding to DLI. These clones were initially identified through analysis of TCR Vβ repertoire (spectratyping), a technique that provides a comprehensive characterization of the circulating T-cell compartment (21 , 24 , 25) . Serial analysis of T-cell repertoire in patient samples has also been used to detect the emergence of oligoclonal and clonal T cells at different times in vivo (18 , 26 , 27) . By combining analysis of TCR repertoire with clinical events, we observed the expansion of individual T-cell clones in peripheral blood that were temporally associated with the initiation of either a GVM or GVHD response (17) . However, despite the association of these T-cell clones with specific clinical responses, the functional specificity of these T cells was not established. Further studies were therefore undertaken to quantify the ...
Yu, Aixin et al "The Lower Limit of Regulatory CD4+ Foxp3+ TCRβ Repertoire Diversity Required To Control Autoimmunity." The Journal of Immunology (2017): 1601966. Web. 23 April. 2018. ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Human cytomegalovirus (HCMV) infections are life-threating to people with a compromised or immature immune system. Upon adhesion, fusion of the virus envelope with the host cell is initiated. In this step, the viral glycoprotein gB is considered to represent the major fusogen. Here, we present for the first time structural data on the binding of an anti-herpes virus antibody and describe the atomic interactions between the antigenic domain Dom-II of HCMV gB and the Fab fragment of the human antibody SM5-1. The crystal structure shows that SM5-1 binds Dom-II almost exclusively via only two CDRs, namely light chain CDR L1 and a 22-residue-long heavy chain CDR H3. Two contiguous segments of Dom-II are targeted by SM5-1, and the combining site includes a hydrophobic pocket on the Dom-II surface that is only partially filled by CDR H3 residues. SM5-1 belongs to a series of sequence-homologous anti-HCMV gB monoclonal antibodies that were isolated from the same donor at a single time point and that ...
0094] "Clonotype profile" means a listing of distinct clonotypes and their relative abundances that are derived from a population of lymphocytes. Typically, the population of lymphocytes are obtained from a tissue sample. The term "clonotype profile" is related to, but more general than, the immunology concept of immune "repertoire" as described in references, such as the following: Arstila et al. Science, 286: 958-61 (1999): Yassai et al. Imnunogenetics, 61: 493-502 (2009); Kedzierska et al, Mol. Immunol., 45(3): 607-618 (2008); and the like. The term "clonotype profile" includes a wide variety of lists and abundances of rearranged immune receptor-encoding nucleic acids, which may be derived from selected subsets of lymphocytes (e.g. tissue-infiltrating lymphocytes, immunophenotypic subsets, or the like), or which may encode portions of immune receptors that have reduced diversity as compared to full immune receptors. In some embodiments, clonotype profiles may comprise at least 103 distinct ...
We will carry out deep sequencing of rearranged immunoglobulin (Ig) and T cell receptor (TCR) genes from lymphocytes in human subjects responding to several dis...
We will carry out deep sequencing of rearranged immunoglobulin (Ig) and T cell receptor (TCR) genes from lymphocytes in human subjects responding to several dis...
Its this seemingly paradoxical and yet crucial yin-and-yang aspect of science that I believe is still quite hard to grasp for non-scientists. Niels Bohr would have appreciated the tension. Bohr bequeathed to the world the concept of complementarity. Complementarity means the existence of seemingly opposite ideas that are still required together to explain the world. In the physical world, complementarity was first glimpsed in the behavior of subatomic particles which can sometimes behave as waves and sometime as particles, depending on the experiment. Waves and particles may seem to be contradictory concepts, and yet as the pioneers of quantum mechanics showed us, you cannot explain reality without assuming that electrons or photons are both. In his later life, Bohr extended the idea of complementarity to many aspects of the human world; good and evil, freedom and restraint, war and peace. He realized that all of these seemingly paradoxical aspects of the human and physical world have to ...
pI profiles across HC CDR3 regions of NZM2410-derived ANAs and non-ANAs. The mean pI value (isoelectric point) at each HC CDR3 position (from H95 to H100a) was
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Immunoglobulins play important roles in antigen recognition during the immune response, and the complementarity-determining region (CDR) 3 of the heavy chain is considered as the critical antigen-binding site. We previously developed a statistical protocol for the extensive analysis of heavy chain variable region repertoires and the dynamics of their immune response using next-generation sequencing (NGS). The properties of important antibody heavy chains predicted in silico by the protocol were examined by gene synthesis and antibody protein expression; however, the corresponding light chain that matches with the heavy chain could not be predicted by our protocol. To understand the dynamics of the heavy chain and the effect of light chain pairing on it, we firstly tried to obtain an artificial light chain that pairs with a broad range of heavy chains and then analyzed its effect on the antigen binding of heavy chains upon pairing. During the pre-B cell stage, the surrogate light chain (SLC) ...
Abs to a number of polysaccharide Ags have several common attributes: CDR-H3 is implicated in binding to Ag (28, 29), its length is strictly maintained (20, 30), and its sequence is almost invariably characterized by the presence of hydrophilic tyrosine residues (21, 31, 32). Xu and Davis (9) showed that, in VH-restricted mice, CDR-H3 diversity was sufficient for the development of specific Ab responses to a variety of hapten and protein Ags but not for two bacterial polysaccharide Ags. The latter finding was attributed to the failure of the single VH gene in their mouse model to accommodate the polysaccharide-specific response, which suggested VH dependency. Work by Nakouzi and Casadevall (33) showed that, in addition to CDR-H3, CDR-H2 encoded amino acids critical for the generation of Abs specific for the polysaccharide galactoxylomannan. These studies highlighted the significant roles that both the VH, as a whole, and the CDR component of the VH, as a part, can play in the generation of ...
Backwash is a ten-year compilation of Wayne Butanes talk-heavy plunderphonics collages. It collects seven cassette recordings and one seven-inch record into one long CDR track. The work is somewhat akin to the less musical side of People Like Us and The Tape Beatles, with emphasis on vocal clips rather than song excerpts - which are also present, but sparse. Like Swipes, which I also reviewed recently, this disc is successful because of its sample diversity - theres so much on here, that you just end up sitting next to the stereo with your mouth gaping open in awe. Sound sources come from everywhere - grisly newscasts, Michael Jackson, Longmont Potion Castle, and even pornography. This isnt nearly as polished as some of the more popular audio collage material, but its a good selection of lo-fi cut-n-pasting. Fun.. 85%. Matt Shimmer ...
We have humanized a murine anti-GM2 MAb in an attempt to improve its potential clinical efficacy by reducing its immunogenicity and by changing the C region to support potent CDC and ADCC. The pharmacokinetic studies of humanized MAbs and murine MAbs in monkeys revealed that the humanization resulted in a prolonged serum half-life and in a substantial reduction in immunogenicity compared with the murine MAbs (44 , 45) . The antihumanized KM8969 response would be theoretically directed to a conformational epitope formed by the CDR loops, so that the reduction in immune response to the KM8969 in monkeys and humans would be expected in comparison with the chimeric KM966, which has murine V regions including CDRs. There has been no comparative pharmacokinetic studies between the humanized MAbs and their counterpart chimeric MAbs. The actual advantages of the humanized MAbs in pharmacokinetics vary for each MAb and need to be evaluated in clinical studies.. The humanized KM8969 showed a binding ...
Repertoire Bibliographique Des Principales Revues Francaises, by Daniel Jordell, 9781236769947, available at Book Depository with free delivery worldwide.
Foot ulceration is one of the most debilitating complications associated with diabetes, but its cause remains poorly understood. Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing. However, few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes. In this study, we analysed the T-cell receptor (TCR) repertoire diversity in TCR-αβ+ T cells. We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers. Our results showed that diabetic individuals, especially those with foot ulcers, have a significantly lower naive T-cell number and a poorer TCR-Vβ repertoire diversity. We also showed that the reduced TCR-Vβ repertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells, the major source of tumour necrosis factor-α production,
social security is sending me too a cdr exam due too not having enough updated information in my medical records also because i havent seen a doctor in 3 years (self medicated with alcohol) so i wanted too know what are my chances of passing the review oct 15 if i start back going too my doctor now or is too late too start back since they already scheduled me a cdr exam and im on ssd for bipolar disorder
deemed to be within a hypervariable region under one set of criteria while being deemed to be outside a hypervariable region under a different set of criteria. One or more of these positions can also be found in extended hypervariable regions (as further defined below). The invention provides antibodies comprising modifications in these hybrid hypervariable positions. In one embodiment, these hybrid hypervariable positions include one or more of positions 26-30,33-35B, 47-49, 57-65, 93,94 and 102 in a heavy chain variable domain. In one embodiment, these hybrid hypervariable positions include one or more of positions 24-29, 35-36,46-49, 56 and 97 in a light chain variable domain. In one embodiment, an antibody of the invention comprises a variant human subgroup consensus framework sequence modified at one or more hybrid hypervariable positions. In one embodiment, an antibody of the invention comprises a heavy chain variable domain comprising a variant human subgroup III consensus framework ...
Looking for Antibody repertoire? Find out information about Antibody repertoire. protein produced by the immune system in response to the presence in the body of antigens: foreign proteins or polysaccharides such as bacteria, bacterial... Explanation of Antibody repertoire
1BZQ: A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops.
Downloadable! Large projects evaluation rises well known difficulties because -by definition- they modify the current price system; their public evaluation presents additional difficulties because they modify too existing shadow prices without the project. This paper analyzes -first- the basic methodologies applied until late 80s., based on the integration of projects in optimization models or, alternatively, based on iterative procedures with information exchange between two organizational levels. New methodologies applied afterwards are based on variational inequalities, bilevel programming and linear or nonlinear complementarity. Their foundations and different applications related with project evaluation are explored. As a matter of fact, these new tools are closely related among them and can treat more complex cases involving -for example- the reaction of agents to policies or the existence of multiple agents in an environment characterized by common functions representing demands or constraints on
1PE8: Conformational Constraint and Structural Complementarity in Thermolysin Inhibitors: Structures of Enzyme Complexes and Conclusions
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Complementarity-determining region - WikipediaComplementarity-determining region - Wikipedia

Complementarity-determining regions (CDRs) are part of the variable chains in immunoglobulins (antibodies) and T cell receptors ... Complementarity determining regions at the US National Library of Medicine Medical Subject Headings (MeSH). ... Framework region Hypervariable region Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology (5th ed.). Saunders, ... these regions are sometimes referred to as hypervariable regions. Within the variable domain, CDR1 and CDR2 are found in the ...
more infohttps://en.wikipedia.org/wiki/Complementarity-determining_region

Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed...Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed...

... the H chain complementarity determining region 3 (CDR3H)3 is the most diverse region in the Ig molecule. Structurally, the CDR3 ... Third complementarity-determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than ... IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two ... Restricted utilization of germ-line VH3 genes and short diverse third complementarity-determining regions (CDR3) in human fetal ...
more infohttps://www.jimmunol.org/content/172/11/6790?ijkey=02e872c3a01f9f6c6f4f9eb40e4d610413d282b5&keytype2=tf_ipsecsha

Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed...Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed...

... the H chain complementarity determining region 3 (CDR3H)3 is the most diverse region in the Ig molecule. Structurally, the CDR3 ... Third complementarity-determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than ... IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two ... Restricted utilization of germ-line VH3 genes and short diverse third complementarity-determining regions (CDR3) in human fetal ...
more infohttps://www.jimmunol.org/content/172/11/6790?ijkey=1d5fa9464e7e8fec6d1d1a951324bd12d0403055&keytype2=tf_ipsecsha

Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell...Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell...

Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell ... Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell ... Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell ... can be activated by complementarity determining region (CDR)-mediated interactions with a variety of autoantigens including BCR ...
more infohttp://www.haematologica.org/content/101/9/e378

The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor...The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor...

The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor ... The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor ... We investigated the role of the complementarity determining region 1 (CDR1) of T cell receptor (TCR) beta chain both in antigen ... These observations demonstrate the participation of the CDR1 region in the recognition of peptide/MHC class I as well as SAg/ ...
more infohttp://jem.rupress.org/content/179/4/1087

The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing...The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing...

The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing ... The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing ... The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing ... The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing ...
more infohttps://jvi.asm.org/content/78/6/3155?ijkey=16f06a14c035f3185c6e7a637c9ca072d886aa33&keytype2=tf_ipsecsha

Dominance of hydrophobic reading frames in complementarity determining region 3 of variable heavy chain genes from a patient...Dominance of hydrophobic reading frames in complementarity determining region 3 of variable heavy chain genes from a patient...

Dominance of hydrophobic reading frames in complementarity determining region 3 of variable heavy chain genes from a patient ... D and J elements of the IgH chains encode the complementarity determining region (CDR) 3 that constitutes a significant part of ...
more infohttps://arthritis-research.biomedcentral.com/articles/10.1186/ar244

Comment on An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regionsComment on An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions

An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions. Anal ... An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions. ... An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions ...
more infohttp://www.bioinfor.com/an-antibody-based-biomarker-discovery-method-by-mass-spectrometry-sequencing-of-complementarity-determining-regions/

JCI -
Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus...JCI - Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus...

Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus cause ... usage and heavy chain complementarity-determining region 3 (H-CDR3) regions of these cloned mAbs to establish whether there are ... However, the heavy chain complementarity-determining region 3 (H-CDR3) of most pathogenic, but not nonpathogenic, mAbs shared ... Randomization of the long H-CDR3 region demonstrates the importance of W for pathogenicity. To determine whether the H-CDR3 ...
more infohttps://6jgc.com.www.mobile.jci.org/articles/view/44425

Lecture 7 (Dustin) - T cells Flashcards by Dustin O | BrainscapeLecture 7 (Dustin) - T cells Flashcards by Dustin O | Brainscape

What region of the TCR does the recognition? CDR: Complementarity Determining Regions ... What helps determine if a naive Th cell will become a Th1 or Th2 cell? ...
more infohttps://www.brainscape.com/flashcards/lecture-7-dustin-t-cells-5479675/packs/8268820

Antibody structure/function (notes/class) Flashcards by Hunter  Garrett | BrainscapeAntibody structure/function (notes/class) Flashcards by Hunter Garrett | Brainscape

complementarity-determining region - CDR1-3. Low variability between hypervariability are * Framework regions (FR1-4) ... regions of Ab which interact with epitope of antigen and idiotype refers to AA sequences w/in variable region of Ab molecule ... Which Ig have a hinge region? What AA is present in the hinge region? ... only constant region of HC is altered. * differences in constant chains of Ab isotypes allows max. versatility of Ab-mediated ...
more infohttps://www.brainscape.com/flashcards/antibody-structure-function-notes-class-375819/packs/804781

Structural basis for autoantibody recognition of phosphatidylserine-β2 glycoprotein I and apoptotic cells | PNASStructural basis for autoantibody recognition of phosphatidylserine-β2 glycoprotein I and apoptotic cells | PNAS

... to Arg was modeled with the combined algorithm for antibody framework alignment and complementarity-determining region (CDR)- ... The initial interaction with a helper T cell then may determine the direction in which B cell specificity may evolve (47), the ... In addition to Arg-53, Arg residues at other sites within the CDR1, CDR2, and one unique location in the third framework region ... 4B), and annexin V-positive and negative cells were analyzed separately to determine the extent of scFv binding and PI staining ...
more infohttps://www.pnas.org/content/98/24/13826?ijkey=7cb90eec6391c0987436ecbb80de47f84600e63d&keytype2=tf_ipsecsha

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein | PNASStructural insights into the antigenicity of myelin oligodendrocyte glycoprotein | PNAS

Interactions of the light chain with MOGIgd are restricted to the complementarity-determining region 1 (CDR1) and to the CDR3 ... The FG loop region of MOGIgd.(a) Superposition of residues 101-108 of free (green) and complexed (yellow) MOGIgd. The Cα trace ... Structure Determination and Analysis. One of the two selenium sites in SeMet-MOGIgd was determined with rsps (13), and ... CDR1 and CDR3 of the 8-18C5 light chain are identical to the corresponding regions of their germ-line sequence (IgVκ 8-28); a ...
more infohttp://www.pnas.org/content/100/16/9446

Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization | JEMPotent and broad neutralization of HIV-1 by a llama antibody elicited by immunization | JEM

Affinity maturation of J3 resulted in a shortened CDR2 (complementarity determining region 2). Analysis of the amino acid ... 6 A) determined for J3 (determined using 23 V genes from L. glama and 7 J genes from Lama pacos [not depicted]). The 23 unique ... J3 amino acid sequence as determined by purified pCAD51 A12 DNA and J3 germline determined based on sequence data (unpublished ... The variable regions (VHH) in these heavy chain-only Abs demonstrate comparable affinity and specificity for antigens to ...
more infohttp://jem.rupress.org/content/early/2012/05/22/jem.20112655

Glossary of biotechnology and genetic engineeringGlossary of biotechnology and genetic engineering

CDR (complementarity-determining regions) These are regions of the variable (V) regions of light and heavy antibody chains that ... adjacent regions of the genome to produce a continuous nucleotide sequence across a chromosomal region. See mapping. ... crown The region at the base of the stem of cereals and forage species from which tillers or branches arise. In woody plants, ... comparative positional candidate gene A gene that is likely to be located in the same region as a DNA marker that has been ...
more infohttp://www.fao.org/docrep/003/X3910E/X3910E06.htm

Category:Immunology - Wikimedia CommonsCategory:Immunology - Wikimedia Commons

Complementarity determining regions‎ (6 D). *. ► Cytokines‎ (17 K, 1 S, 102 D) ...
more infohttps://commons.wikimedia.org/wiki/Category:Immunology?uselang=als

Category:Immunology - Wikimedia CommonsCategory:Immunology - Wikimedia Commons

Complementarity determining regions‎ (6 B). *. ► Cytokines‎ (17 C, 1 P, 98 B) ...
more infohttps://commons.wikimedia.org/wiki/Category:Immunology?uselang=nl

JCI -
Homeostatic control of immunity by TCR peptide-specific TregsJCI - Homeostatic control of immunity by TCR peptide-specific Tregs

TCR peptides derived mostly from the conserved complementarity determining region (CDR) and framework (Fr) regions of the TCR V ... Nonstandard abbreviations used: CDR, complementarity determining region; EAE, experimental autoimmune encephalomyelitis; Fr, ... β framework or in the CDR1/2 regions. Examination of these determinants in the Fr3 and CDR2 regions of the Vβ8.2 chain suggests ... it is clear that peptides from 2 distinct conserved regions, namely the Fr3 and CDR1/2 regions on the TCR Vβ8.2 chain, can ...
more infohttps://www.jci.org/articles/view/23166

Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate,...Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate,...

DNA sequences of the third complementarity determining regions were identified. This approach is based on subcutaneous melanoma ... or YAC-1 cells was determined by standard 51Cr-release assay. B16OVA cells were subjected to hyperthermia using NPrCAP/M with ...
more infohttps://www.hindawi.com/journals/jsc/2013/742925/

One-Step Recovery of scFv Clones from High-Throughput Sequencing-Based Screening of Phage Display Libraries Challenged to Cells...One-Step Recovery of scFv Clones from High-Throughput Sequencing-Based Screening of Phage Display Libraries Challenged to Cells...

This method was applied to some scFv fragments, characterized by heavy-chain complementarity determining regions 3 (HCDR3) of ... Light chain variable region.. Conflict of Interests. The authors declare that there is no conflict of interests regarding the ... Figure 3(b) shows that the isolated VH and VL regions of these clones actually generate full antibodies. They were also tested ... Sanger sequencing of the recovered 3_2, 3_5, and 3_67 clones confirmed 100% identity of the VH regions to the HTS data for each ...
more infohttps://www.hindawi.com/journals/bmri/2015/703213/

JCI -
In vivo correction of ZAP-70 immunodeficiency by intrathymic 
gene transferJCI - In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer

The Immunoscope method is based on an RT-PCR of the hypervariable complementarity determining region 3 (CDR3), which allows the ... Nonstandard abbreviations used: ADA, adenosine deaminase; BV, β chain hypervariable region; CDR3, complementarity determining ... LTR deleted of 400 bp in the U3 region (29); U3, untranslated 3′ region of the LTR; and R, repeated region of the LTR. ... B) The activation status of the T cell population was determined using PE-conjugated α-CD25 and α-CD69 mAbs, and the relative ...
more infohttps://jci.org/articles/view/23966

Frontiers | Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy | ImmunologyFrontiers | Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy | Immunology

The TCRα- and β-chains possess three hypervariable regions, referred to as complementarity-determining regions (CDR) 1, 2, and ... ACT, adoptive cell transfer; CDR, complementarity-determining region; CTL, cytotoxic T lymphocyte; CTLA, cytotoxic T-lymphocyte ... Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (2015) 348(6230):124-8. doi ... Pannetier C, Cochet M, Darche S, Casrouge A, Zoller M, Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2018.00014/full

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.  - PubMed - NCBISequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice. - PubMed - NCBI

Antibody regions are indicated in gray. FR= framework region; CDR= complementarity determining region. Amino acid position is ... Framework regions (FWR) are shaded in gray and white areas correspond to complementarity determining regions (CDRs). Nt= ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/27610569

Frontiers | Novel Antibody Drug Conjugates Targeting Tumor-Associated Receptor Tyrosine Kinase ROR2 by Functional Screening of...Frontiers | Novel Antibody Drug Conjugates Targeting Tumor-Associated Receptor Tyrosine Kinase ROR2 by Functional Screening of...

FR, framework region; CDR, complementarity-determining region. Dashes indicate gaps due to the alignment. ... Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with ... VL coding regions were amplified using VL (kappa) forward primers and Igκ light chain constant region-specific reverse primers ... such that the mice primarily generate chimeric antibodies encoded by fully human VH and VL regions and rat constant regions. ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02490/full

TRB@ | Cancer Genetics Web[email protected] | Cancer Genetics Web

Pretreatment samples were used to define clonal T cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, ... and its relation with the third complementary-determining region gene spectratyping of TCRVβ-chain (TCRVβCDR3).. METHODS: Rats ... and the common gained region (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans a smaller region ... This region represents the germline organization of the T cell receptor beta locus. The beta locus includes V (variable), J ( ...
more infohttp://www.cancerindex.org/geneweb/TRB.htm
  • To examine the structural basis of the pathogenic autoantibody response to MOG we determined the crystal structures of the extracellular domain of rat MOG (residues 1-126, MOG Igd ) and a complex of MOG Igd with the chimeric antigen-binding fragment (Fab) of the demyelinating MOG-specific monoclonal antibody 8-18C5 ( 8 ). (pnas.org)
  • These studies indicate that H-CDR3 is critical for pathogenicity of a human autoantibody, that a small region (even 1 amino acid) can mediate pathogenicity, and that pathogenicity can be uncoupled from binding in these antibodies. (jci.org)
  • The lengths of the FR-IMGT and CDR-IMGT are in themselves crucial information which characterize variable regions belonging to a group, a subgroup and/or a gene [2- (imgt.org)
  • This method is usually straightforward in the V H and J H regions, where there are large regions of sequence similarity. (jimmunol.org)
  • The core epitope of 2F5, the most studied of the two MAbs, has been defined conveniently by a short linear sequence, ELDKWA, which is found at the extreme C-terminal end of the C-heptad repeat region on the ectodomain of gp41 ( 37 ). (asm.org)