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.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.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).Cytidine Deaminase: An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.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.Somatic Hypermutation, Immunoglobulin: A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development.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.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.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).Cyclospora: A genus of coccidian parasites in the family EIMERIIDAE. Cyclospora cayetanensis is pathogenic in humans, probably transmitted via the fecal-oral route, and causes nausea and diarrhea.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.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.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).Genetic Variation: Genotypic differences observed among individuals in a population.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.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.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.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Biodiversity: The variety of all native living organisms and their various forms and interrelationships.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Epitopes: Sites on an antigen that interact with specific antibodies.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).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.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Antibodies, Bispecific: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.Mice, Inbred BALB CSingle-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.Antibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.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.Immunoglobulin 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.Cultural Diversity: Coexistence of numerous distinct ethnic, racial, religious, or cultural groups within one social unit, organization, or population. (From American Heritage Dictionary, 2d college ed., 1982, p955)

Gene conversion and hypermutation during diversification of VH sequences in developing splenic germinal centers of immunized rabbits. (1/350)

The young rabbit appendix and the chicken bursa of Fabricius are primary lymphoid organs where the B cell Ab repertoire develops in germinal centers (GCs) mainly by a gene conversion-like process. In human and mouse, V-gene diversification by somatic hypermutation in GCs of secondary lymphoid organs leads to affinity maturation. We asked whether gene conversion, somatic hypermutation, or both occur in rabbit splenic GCs during responses to the hapten DNP. We determined DNA sequences of rearranged heavy and light chain V region gene segments in single cells from developing DNP-specific GCs after immunization with DNP-bovine gamma-globulin and conclude that the changes at the DNA level that may lead to affinity maturation occur by both gene conversion and hypermutation. Selection was suggested by finding some recurrent amino acid replacements that may contribute increased affinity for antigen in the complementarity-determining region sequences of independently evolved clones, and a narrower range of complementarity-determining region 3 lengths at day 15. Some of the alterations of sequence may also lead to new members of the B cell repertoire in adult rabbits comparable with those produced in gut associated lymphoid tissues of young rabbits.  (+info)

Antigen-induced somatic diversification of rabbit IgH genes: gene conversion and point mutation. (2/350)

During T cell-dependent immune responses in mouse and human, Ig genes diversify by somatic hypermutation within germinal centers. Rabbits, in addition to using somatic hypermutation to diversify their IgH genes, use a somatic gene conversion-like mechanism, which involves homologous recombination between upstream VH gene segments and the rearranged VDJ genes. Somatic gene conversion and somatic hypermutation occur in young rabbit gut-associated lymphoid tissue and are thought to diversify a primary Ab repertoire that is otherwise limited by preferential VH gene segment utilization. Because somatic gene conversion is rarely found within Ig genes during immune responses in mouse and human, we investigated whether gene conversion in rabbit also occurs during specific immune responses, in a location other than gut-associated lymphoid tissue. We analyzed clonally related VDJ genes from popliteal lymph node B cells responding to primary, secondary, and tertiary immunization with the hapten FITC coupled to a protein carrier. Clonally related VDJ gene sequences were derived from FITC-specific hybridomas, as well as from Ag-induced germinal centers of the popliteal lymph node. By analyzing the nature of mutations within these clonally related VDJ gene sequences, we found evidence not only of ongoing somatic hypermutation, but also of ongoing somatic gene conversion. Thus in rabbit, both somatic gene conversion and somatic hypermutation occur during the course of an immune response.  (+info)

Secondary rearrangements and hypermutation generate sufficient B cell diversity to mount protective antiviral immunoglobulin responses. (3/350)

Variable (V) region gene replacement was recently implicated in B cell repertoire diversification, but the contribution of this mechanism to antibody responses is still unknown. To investigate the role of V gene replacements in the generation of antigen-specific antibodies, we analyzed antiviral immunoglobulin responses of "quasimonoclonal" (QM) mice. The B cells of QM mice are genetically committed to exclusively express the anti-(4-hydroxy-3-nitrophenyl) acetyl specificity. However, approximately 20% of the peripheral B cells of QM mice undergo secondary rearrangements and thereby potentially acquire new specificities. QM mice infected with vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus, or poliovirus mounted virus-specific neutralizing antibody responses. In general, kinetics of the antiviral immunoglobulin responses were delayed in QM mice; however, titers similar to control animals were eventually produced that were sufficient to protect against VSV-induced lethal disease. VSV neutralizing single-chain Fv fragments isolated from phage display libraries constructed from QM mice showed VH gene replacements and extensive hypermutation. Thus, our data demonstrate that secondary rearrangements and hypermutation can generate sufficient B cell diversity in QM mice to mount protective antiviral antibody responses, suggesting that these mechanisms might also contribute to the diversification of the B cell repertoire of normal mice.  (+info)

Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice. (4/350)

Fetal Igs are less diverse than adult Igs, largely because of the lack of N addition in the absence of Tdt. To test whether the absence of Tdt is essential, we generated Tg mice that express Tdt and add N regions in fetal B cells. When challenged as adults with PC-containing Streptococcus pneumoniae, these mice fail to make the hallmark T15 anti-PC Ab encoded by canonical rearrangements of Ig H and L chain genes. The anti-PC Abs from these mice are altered by premature N addition and do not protect against death from virulent pneumococcal infection. These results show that maintenance of lower Ig diversity in early life is essential for the acquisition of a complete functional adult repertoire.  (+info)

Functional diversity of natural IgM. (5/350)

This paper proposes a method for the quantitative characterization of repertoire diversity of an unknown mixture of antibodies on the basis of its reactivity profile in the quantitative immunoblot (QIB). The QIB is calibrated by measuring the reactivity profiles of supernatants of known 'diversity' (i.e. known numbers of B cell clones). We define a quantitative 'index of variability' (IV) which decreases regularly as the diversity increases and the profiles tend towards a common 'convergence profile'. The calibration procedure is consolidated by a mathematical model based on the Poisson distribution; this theoretical model accounts correctly for the observed convergence behavior. On the basis of this calibration curve, it is possible to estimate the diversity of an unknown antibody mixture from a measure of its IV. We conclude that the functional diversity of natural serum IgM in mice can be estimated at approximately 16,000 clones.  (+info)

B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions. (6/350)

Multiple sclerosis (MS) lesions in the CNS are characterized by disseminated demyelination with perivascular infiltrates of macrophages, T cells, and B cells. To investigate the origin and characteristics of the B cell population found in MS plaque tissue, we performed molecular studies in 10 MS patients and 4 non-MS control samples. Ig transcripts from the perivascular infiltrated brain lesions were analyzed by complementary-determining region 3 spectratyping to ascertain the B cell heavy chain gene rearrangement repertoire expressed in MS brains. Significant rearrangement diversity and deviation from the normal Ig heavy (H) chain repertoire was observed. The cloning and sequencing of RT-PCR products from families VH1 and VH4 showed a correlation with the profiles obtained by spectratyping. Generally, restricted spectratyping patterns concurred with repetition of in-frame complementary-determining region 3 identical sequences. The analysis of heavy chain variable (VH), diversity (D), and joining (JH) gene segments revealed the increased usage of VH1-69, VH4-34, and VH4-39. Similarly, gene segments from families D2, D3, and JH4 were over-represented. The presence of restricted patterns of rearranged Ig mRNA within the plaque lesion suggests that Ab production in the demyelinating plaque is a local phenomenon and supports the idea that in MS an Ag-driven immune response might be responsible for demyelination.  (+info)

Efficient antibody diversification by gene conversion in vivo in the absence of selection for V(D)J-encoded determinants. (7/350)

Antibody diversification in the bursa of Fabricius occurs by gene conversion: pseudogene-derived sequences replace homologous sequences in rearranged immunoglobulin genes. Bursal cells expressing a truncated immunoglobulin mu heavy chain, introduced by retroviral gene transfer, bypass normal requirements for endogenous surface immunoglobulin expression. Immunoglobulin light chain rearrangements in such cells undergo gene conversion under conditions where the products are not selected based on their ability to encode a functional protein. The efficiency with which gene conversion maintains a productive reading frame exceeds 97% under such non-selective conditions. By analysis of donor pseudogene usage we demonstrate that bursal cell development is not driven by a restricted set of antigenic specificities. We further demonstrate that gene conversion can restore a productive reading frame to out-of-frame VJ(L) junctions, providing a rationale for the elimination of cells containing non-productive VJ(L) rearrangements prior to the onset of gene conversion in normal bursal cell development.  (+info)

Antibody repertoires of four- and five-feature translocus mice carrying human immunoglobulin heavy chain and kappa and lambda light chain yeast artificial chromosomes. (8/350)

We have produced mice that carry the human Ig heavy (IgH) and both kappa and lambda light chain transloci in a background in which the endogenous IgH and kappa loci have been inactivated. The B lymphocyte population in these translocus mice is restored to about one-third of normal levels, with preferential (3:1) expression of human lambda over human kappa. Human IgM is found in the serum at levels between 50 and 400 microg/ml and is elevated following immunization. This primary human Ab repertoire is sufficient to yield diverse Ag-specific responses as judged by analysis of mAbs. The use of DH and J segments is similar to that seen in human B cells, with an analogous pattern of N nucleotide insertion. Maturation of the response is accompanied by somatic hypermutation, which is particularly effective in the light chain transloci. These mice therefore allow the production of Ag-specific repertoires of both IgM,kappa and IgM,lambda Abs and should prove useful for the production of human mAbs for clinical use.  (+info)

*Ancestral reconstruction

Gaschen, B. (2002). "Diversity Considerations in HIV-1 Vaccine Selection". Science. 296 (5577): 2354-2360. doi:10.1126/science. ... "Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in ... Today, computational methods for ancestral reconstruction continue to be extended and applied in a diversity of settings, so ... Ridley, Mark (1983). The explanation of organic diversity: the comparative method and adaptations for mating. Oxford: Clarendon ...

*Gabriel Victora

"Tracking Antibody Diversity". NIH Director's Early Independence Award Highlights. National Institutes of Health. Retrieved 2017 ... Independence Award for his work using colored tags to understand the changes over time of the level of diversity of antibodies ...

*Immunoglobulin heavy chain

"Reshaping Antibody Diversity". Cell. 153 (6): 1379-93. doi:10.1016/j.cell.2013.04.049. PMC 4007204 . PMID 23746848. Fish heavy ... The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of an antibody (immunoglobulin). A typical antibody is ... an antibody lacking light chains, and can be used to produce single-domain antibodies, which are essentially the variable ... The resulting antibody, IgM, is secreted as a tetramer in teleost fish instead of the typical pentamer found in mammals and ...

*Susumu Tonegawa

Somatic generation of antibody diversity. Nature, 302(5909), 575-581. Gillies, S. D., Morrison, S. L., Oi, V. T., & Tonegawa, S ... for his discovery of the genetic mechanism that produces antibody diversity. Although he won the Nobel Prize for his work in ... and deleted to form the diversity of the variable region of antibodies. In 1983, Tonegawa also discovered a transcriptional ... In experiments beginning in 1976, Tonegawa showed that genetic material rearranges itself to form millions of antibodies. ...

*Colworth Medal

Williamson, A. R. (1972). "Extent and control of antibody diversity". The Biochemical Journal. 130 (2): 325-33. doi:10.1042/ ...

*Chemical specificity

"Chemical basis for antibody diversity and specificity". Accounts of Chemical Research. 1 (6): 161-167. doi:10.1021/ar50006a001 ... Antibodies are specific to the target protein of interest, and will contain a fluorescent tag signaling the presence of the ... An example of a protein-ligand pair whose binding activity can be described as highly specific is the antibody-antigen system. ... Immunostaining utilizes the chemical specificity of antibodies in order to detect a protein of interest at the cellular level. ...

*DNA mismatch repair

Chahwan, Richard; Edelmann, Winfried; Scharff, Matthew D; Roa, Sergio (August 2012). "AIDing antibody diversity by error-prone ... where POLH is used to introduce genetic variation into antibody genes. However, this error-prone MMR pathway may be triggered ...

*Somatic hypermutation

Li, Z.; Wool, C.J.; Iglesias-Ussel; M.D., Ronai, D.; Scharff, M.D. (2004). "The generation of antibody diversity through ... ISBN 0-8153-4101-6. Oprea, M. (1999) Antibody Repertoires and Pathogen Recognition: The Role of Germline Diversity and Somatic ... The B cells with the greatest affinity will then be selected to differentiate into plasma cells producing antibody and long- ... Origin of congenital defects: stable inheritance through the male line via maternal antibodies specific for eye lens antigens ...

*Leroy Hood

"1987 Albert Lasker Basic Medical Research Award Genetic basis of antibody diversity". Albert And Mary Lasker Foundation built ... Rees, Anthony R. (2015). The Antibody Molecule: From Antitoxins to Therapeutic Antibodies. Oxford University Press. pp. 104-120 ... Dreyer on antibody diversity. Dreyer is credited with giving Hood two important pieces of advice: "If you want to practice ... conducted pioneering studies on the structure and diversity of the antibody genes. This research led to verification of the " ...

*Organization and expression of immunoglobulin genes

... antibody molecule play important role in antibody diversity and production of different subclasses or classes of antibodies. ... Antibody diversity is produced by genetic rearrangement after shuffling and rejoining one of each of the various gene segments ... These errors are one of the sources of the antibody diversity that is commonly observed in both the light and heavy chains. ... The high concentrations of these mutations at the variable region also produce high antibody diversity. When the B cells get ...

*Transposable element

TEs may also have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J ... November 2009). "The B73 maize genome: complexity, diversity, and dynamics". Science. 326 (5956): 1112-1115. Bibcode:2009Sci... ...

*Alcino J. Silva

Susumu Tomegawa was awarded a Nobel Prize in 1987 for his discovery of the genetic mechanism that produces antibody diversity. ...

*Activation-induced cytidine deaminase

In B cells in the lymph nodes, AID causes mutations that produce antibody diversity, but that same mutation process leads to B ... in which the antibody genes are minimally mutated to generate a library of antibody variants, some of which with higher ... AID is currently thought to be the master regulator of secondary antibody diversification. It is involved in the initiation of ... Petersen-Mahrt SK, Harris RS, Neuberger MS (2002). "AID mutates E. coli suggesting a DNA deamination mechanism for antibody ...

*V(D)J recombination

... "for his discovery of the genetic principle for generation of antibody diversity". Human antibody molecules (and B cell ... Antibody B cell B cell receptor T cell T cell receptor Recombination-activating gene NKT cell "The Nobel Prize in Physiology or ... The T cell receptor in this sense is the topological equivalent to an antigen-binding fragment of the antibody, both being part ... DNA rearrangement causes one copy of each type of gene segment to go in any given lymphocyte, generating an enormous antibody ...

*César Milstein

Milstein's early work on antibodies focused on the nature of their diversity at the amino acid level as well as on the ... of Milstein's research career was devoted to studying the structure of antibodies and the mechanism by which antibody diversity ... Quite apart from his own achievements, Milstein acted as a guide and inspiration to many in the antibody field as well as ... The emphasis of his research then shifted towards the mRNA encoding antibodies where he was able to provide the first evidence ...

*Riken

... and winner of the 1987 Nobel Prize for Physiology or Medicine for his discovery of the mechanism of antibody diversity. Michiyo ...

*Georges J. F. Köhler

Köhler remained at the Basel Institute for another nine years, during which time he continued investigating antibody diversity ... Milstein and Köhler's technique for producing monoclonal antibodies laid the foundation for the exploitation of antibodies for ... Milstein to develop a laboratory tool that could help them investigate the mechanism that underlies the diversity of antibodies ... It was during this work that they devised their hybridoma technique for the production of antibodies. Köhler continued his ...

*List of biologists

... "discovery of the genetic principle for generation of antibody diversity" John Torrey (1796-1873), American botanist, first ...

*Xmap

... antibody diversity profiling, antibody identification or histocompatibility screen etc. ...

*List of MeSH codes (G13)

... antibody diversity MeSH G13.920.073 --- antigenic variation MeSH G13.920.331 --- genetic heterogeneity MeSH G13.920.590 --- ...

*List of MeSH codes (G04)

... antibody diversity MeSH G04.610.626.073 --- antigenic variation MeSH G04.610.626.320 --- gene rearrangement, b-lymphocyte MeSH ... antibody affinity MeSH G04.610.143.140 --- antigenic modulation MeSH G04.610.143.232 --- binding sites, antibody MeSH G04.610. ... antibody-dependent cell cytotoxicity MeSH G04.610.270.500 --- macrophage activation MeSH G04.610.484.100 --- clonal anergy MeSH ... antibody-dependent enhancement MeSH G04.185.515.880.210 --- cell transformation, viral MeSH G04.185.515.880.225 --- ...

*List of geneticists

Nobel Prize for genetics of antibody diversity Erich von Tschermak (1871-1962) Austrian agronomist and one of the re- ... antibody-combining sites Henrik Kacser (1918-1995), Romanian-born UK biochemist and geneticist, worked on metabolic control ... transposable elements re genetic diversity Raymond L. White, US cancer geneticist, cloned APC colon cancer gene and ... Nobel Prize for hybridomas making monoclonal antibodies Arthur Kornberg (born 1918), US biochemist, Nobel Prize on DNA ...

*Antibody

This serves to increase the diversity of the antibody pool and impacts the antibody's antigen-binding affinity. Some point ... Magnetic immunoassay Microantibody Monoclonal antibody Neutralizing antibody Secondary antibodies Single-domain antibody Slope ... Affimer Antibody mimetic Anti-mitochondrial antibodies Anti-nuclear antibodies Aptamer Colostrum ELISA Humoral immunity ... Nucleic acids and small molecules are sometimes considered antibody mimetics, but not artificial antibodies, antibody fragments ...

*Polymerase

Other well-known polymerases include: Terminal Deoxynucleotidyl Transferase (TDT), which lends diversity to antibody heavy ...

*Germ line theory

It was clear that there should be a mechanism that help the antibody to have diversity and keep it constant. The germ line ... The germ-line theory was a proposed explanation for immunoglobulin diversity that proposed that each antibody was encoded in a ... For decades microbiologists searched for a mechanism that could explain the large diversity of antibody structure. For this ...

*Phage display

... thereby allowing human antibodies to be created in vitro from synthetic diversity elements. Antibody libraries displaying ... Antibody phage display was later used by Carlos F. Barbas at The Scripps Research Institute to create synthetic human antibody ... HUMIRA, an antibody to TNF alpha, was the world's first fully human antibody, which achieved annual sales exceeding $1bn. Below ... The invention of antibody phage display revolutionised antibody drug discovery. Initial work was done by laboratories at the ...

*Clonal selection

In short the theory is an explanation of the mechanism for the generation of diversity of antibody specificity. The first ... In 1957, David W. Talmage hypothesized that antigens bind to antibodies on the surface of antibody-producing cells and "only ... in an attempt to explain the formation of a diversity of antibodies during initiation of the immune response. The theory has ... The entrance of an antigen into the body results in the selection of only one type of antibody to match it. This may happen by ...
Generation of Antibody Diversity. The big question:how do you get all those different antibodies? Two other big questions- getting different classes with the same variable regions, and getting secreted and membrane-bound forms of the same class Slideshow 6869117 by amal-herring
Combinatorial association of immunoglobulin gene elements is the most important process in the creation of extreme diversity of antibody molecules. The recombination of germ-line variable gene elements V, D, and J can potentially generate approximately 6000 variable genes of human heavy chains. As joining of these elements is imprecise and is occurring with nucleotide additions or deletions, the created diversity is in fact much higher. The assembled variable genes can be revised and edited resulting in a change of their affinity and even specificity. Due to somatic hypermutation, the affinity of synthesized antibody increases even more. Another variant of combinatorial recombination is joining of complete variable genes with one of the several constant genes and the formation of various immunoglobulin isotypes with different effector functions but with the same antibody specificity. Consequently, these processes not only develop the antibody repertoire but also solve some other problems of the adaptive
B cells, the elite soldiers of the bodys immune system serve as an army that is ready to recognize and destroy the invading antigens
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
Collagen is a main structural protein found in our bodies. Though replacement products are growing in popularity, will they really take ages off your skin?
Sequence analysis revealed that S1 mAbs displayed between 85-95% and 89-97% germline identity for heavy and light chains, respectively (Fig. 2C). Analyses of germline gene usage and V(D)J recombination indicate that they originate from different B cell lineages. The role of somatic hypermutations for the two most potent antibodies, mAb100 and mAb114, were analyzed using variants that were partially or completely reverted to the unmutated common ancestors (UCAs) (Fig. 2D and fig. S4, A and B). The fully reverted mAb100 (UCA/UCA), as well as a variant with a single change from the UCA VL (UCA/gL, A89T), recognized cells expressing GP with 2-4 fold weaker binding compared with the fully matured antibody (Fig. 2Eand fig. S4, A and B). When three HCDR3 mutations (A96V/V103Y/Y114S) were introduced in the reverted germline antibody (gH/UCA), binding was comparable to the fully matured mAb100 (sH/sL) suggesting that three mutations are sufficient to confer the binding observed for the fully matured ...
The intestinal commensal microbiota is required for development of lymphoid tissues and mucosal immunity in vertebrates. However, little is known of the mechani...
The analysis of B cell development and diversification in humans is problematic and, to a degree, has been inferred from analyses of other mammalian species. However, nature often provides material that is every bit as informative as that generated by laboratory geneticists. One example is patients with common variable immune deficiencies (CVIDs). Among this heterogeneous group are individuals with mutations in key genes required for the formation of GCs (11), which, as mentioned, are sites of antigen-driven repertoire diversification mediated by V gene SHM (1, 2). GC B cell survival and entry into the memory compartments is selective and depends on the affinity with which their receptors bind antigen (12), with higher affinity cells expanding preferentially. This antigen-mediated selection results in a distribution of mutations in the V gene segments of memory B cells that is significantly different from the distribution that would be predicted if mutations were inserted at random; changes ...
BOSTON - As elite soldiers of the bodys immune response, B cells serve as a vast standing army ready to recognize and destroy invading antigens, including infections and cancer cells. To do so, each new B cell comes equipped with its own highly specialized weapon, a unique antibody protein that selectively binds to specific parts of the antigen. The key to this specialization is the antigen-binding region that tailors each B cell to a particular antigen, determining whether B cells survive boot camp and are selected for maturation and survival, or wash out and die.. Now, using high-throughput sequencing technology and computational and systems biology, investigators from Beth Israel Deaconess Medical Center (BIDMC) have discovered that B cells can be selected for survival independent of their antigen binding regions. Described online this week in the journal Proceedings of the National Academy of Sciences (PNAS), the findings add a surprising new dimension to the understanding of antibody ...
For his imaginative studies of somatic recombination in the immune system, showing that rearrangements of genes lead to an infinite diversity of antibodies.
Antibodies are key molecules of the adaptive immune response and are now a major class of biopharmaceuticals. Pairing of heavy and light chains is one of the ways of generating antibody diversity and, while little is known about mechanisms governing V(H)/V(L) pairing, previous studies have suggested that the germline source from which chains are paired is random. By selecting paired antibody protein sequences from human and mouse antibodies from the KabatMan database and mapping them onto their corresponding germline sequences, we find that pairing preferences do exist in the germline, but only for a small proportion of germline gene segments; others are much more promiscuous showing no preferences. The closest equivalent human and mouse gene families were identified and pairing preferences compared. This work may impact on the ability to generate more stable antibodies for use as biopharmaceuticals.
E) Innate and adaptive immune system Cells and molecules involved in innate and adaptive immunity, antigens, antigenicity and immunogenicity. B and T cell epitopes, structure and function of antibody molecules. generation of antibody diversity, monoclonal antibodies, antibody engineering, antigen-antibody interactions, MHC molecules, antigen processing and presentation, activation and differentiation of B and T cells, B and T cell receptors, humoral and cell-mediated immune responses, primary and secondary immune modulation, the complement system, Toll-like receptors, cell-mediated effector functions, inflammation, hypersensitivity and autoimmunity, immune response during bacterial (tuberculosis), parasitic (malaria) and viral (HIV) infections, congenital and acquired immunodeficiencies, vaccines. ...
This course is an introductory study of the biological and clinical approaches to immunology. Discussions center on the mechanisms responsible for various clinical syndromes as well as basic immunological phenomena such as antibody diversity, T cell receptor diversity, antigen presentation, signaling across cellular receptors, and cell activation. This course includes one semester hour credit for laboratory sessions. (Offered also as BIOL 4464.). ...
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Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the immunoglobulin (Ig) M, IgG, and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n [ 16) in comparison with healthy controls (HCs; n [ 16). The Complementary Determining Region 3 region of the immunoglobulin heavy chain variable region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis, and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show interindividual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B-cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p [ 0.01). ...
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The continuous ileal Peyers patches (IPP) of sheep are regarded as a type of mammalian bursal equivalent where B cells diversify their repertoire in an Ag-independent fashion. Anatomically and developmentally similar IPP occur in swine. Resection of ∼90% of the IPP in piglets at birth did not alter Ig levels in serum and secretions or retard diversification of the Ab repertoire when animals were maintained in isolators and colonized with a defined gut flora. Resection or sham surgery elevated IgG and IgA in serum and in lavage fluid from the gut, lung, and in saliva. No changes in the frequency of IgG-, IgA-, and IgM-containing cells in the spleen and peripheral lymph node were observed. Using an index that quantifies diversification of the VDJ repertoire, no differences were seen in three secondary lymphoid tissues between piglets lacking IPP and colonized controls, whereas both groups displayed ,10-fold greater diversification than did late-term fetal piglets or piglets maintained ...
Kohler and Milstein used novel in vitro techniques to combine the immortality of non-secretary myeloma cells with immune B cells to produce "hybridomas"-immortalised biological factories capable of producing monoclonal antibodies. By prior immunisation of mice, and subsequent selection of splenic B cells producing desired antibody specificity, "designer" antibodies had arrived.. By 1987, Tonegawa had defined "the genetic principle for the generation of antibody diversity". In the 1970s he solved the paradox of how our limited genetic material is capable of generating almost limitless diversity. On the chromosome where the presumed "light" chain gene was expected to be located, he found not one single gene, but rather, a series of V (variable) and J (joining) genes. After removal of the intervening segment of DNA, any random combination of these genes allows the generation of many alternative light chains. Subsequent studies showed that equivalent V, J, and D (diversity) genes on the heavy chain ...
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After receiving my Ph.D. studying the structure and function of eukaryotic genes, I chose to focus my research career in the field of Immunology. During my postdoctoral fellowship with Dr. Malcolm Gefter at MIT, I made important contributions to our understanding of the genetic basis for development of antibody diversity during primary and antigen-driven B cell development. My main research interest since that time has been to elucidate the molecular and cellular basis for immune memory and self tolerance in the B cell compartment. My laboratory has extensive utilized mouse model systems and mouse reversed genetics approaches to address these questions for over 25 years. In recent years, we have concentrated on the role of the germinal center in the antigen receptor diversification and selection events that culminate in the development of the memory B cell compartment. To begin to translate the discoveries we have made in mouse model systems to a better understanding of the development of immune ...
Antibody diversification through non-VDJ insertions Mikhail Lebedin (AG De La Rosa (MDC))DNA replication associated Genome instability and its implications in carcinogenesis and therapy Sandhya Balasubramanian (AG Di Virgilio (MDC))
Activation-induced deaminase (AID) is expressed only in germinal center B cells. There, it is required for somatic hypermutation, gene conversion and class switch recombination of antibody variable region segments, three processes that diversify antibodies during immune responses. Although AID has homology to RNA-editing enzymes, three recent reports suggest it could initiate the diversification processes by deaminating cytidine residues within the antibody genes themselves.
Lower vertebrate species, including Xenopus laevis, exhibit restricted antibody diversity relative to higher vertebrates. We have analyzed more than 180 VH gene-containing recombinant clones from an unamplified spleen cDNA library by selective sequencing of JH and CH positive clones following iterative hybridization screening with family-specific VH probes, 11 unique families of VH genes, each associated with a unique genomic Southern blot hybridization pattern, are described and compared. Considerable variation in the number of hybridizing components detected by each probe is evident. The nucleotide sequence difference between VH families is as great as, if not more than, that reported in other systems, including representatives of the mammalian, avian, and elasmobranch lineages. Some Xenopus Ig gene families encode alternative amino acids at positions that are otherwise invariant or very rarely substituted in known Igs. Furthermore, variations in complementarity determining region sequences ...
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Activation-Induced cytidine deaminase (AID) is expressed in germinal center B cells and is required for somatic hypermutation (SHM) and class switch recombinati...
Human monoclonal antibodies often display limited thermodynamic and colloidal stabilities. This behavior hinders their production, and places limitations on the development of novel formulation conditions and therapeutic applications. Antibodies are highly diverse molecules, with much of the sequence variation observed within variable domain families and, in particular, their complementarity determining regions. This has complicated the development of comprehensive strategies for the stability engineering of the human antibody repertoire. Here we provide an overview of the field, and discuss recent advances in the development of robust and aggregation resistant antibody therapeutics.
Maju: Dienekes is technically correct. All we have to sort people into piles is SNPs. To date there has been a relatively sparse number and people have been erroneously put in "clusters". As you say the more STR markers looked at, the lesser the chance. I think the mutation rate of the founders mutation is important since slow mutators are less likely to have many "random" occurrences. TMRCA analysis can also help by showing that the number of mutations the questionable entry has fits in with the core group?? In the Ian Cam, it ranges from zero in 700 years to 6 or 7 over 67. They all fit within the TMRCA timeframe of the founder. This is why I say that you cant look at one individual and make that decision, it is the combined mutations of the whole group that tells the truth. Names, certainly dont work. In the Ian Cam we have Stirlings who, many of which, are genetically MacGregors. The history of the clan is that the name was proscribed by the British for almost two hundred years. Clan ...
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
The research in my laboratory focuses on the development of genetic strategies for the control of pest insect species. One important aspect of this is the use of gene vectors that efficiently introduce genes into these species. These gene vectors must be robust enough to allow the high frequency transformation of a target insect species yet be able to be easily manipulated so they can function as effective genetic tools. Transposable elements are small pieces of DNA that can move within and between genomes and some of these have been developed as rudimentary gene vectors in some insect species. We have participated in the isolation and development of two such transposable elements, the Hermes element from the housefly, Musca domestica and the Herves element from the malaria mosquito, Anopheles gambiae. Both are members of the hAT superfamily of transposable elements and this superfamily is related to V(D)J recombination system that is largely responsible for generating antibody diversity in the ...
Research focus includes statistical methods for bioassays (e.g., flow cytometry, sequencing); dynamic modeling of biological systems (e.g., multi-type cell populations, B-cell repertoire); nonparametric methods for supervised and unsupervised learning; stochastic processes (e.g., branching processes); algorithms for scalable data analysis.
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A significant leap forward got here in 2000 with the invention that activation-induced deaminase (AID) is actually required for hypermutation. This used to be in 2002 by means of proof that reduction without delay edits the DNA that encodes an antibody in an activated B mobile. a lot has seeing that been learnt concerning the biochemistry and rules of reduction, however the mechanism during which it truly is recruited particularly to antibody-encoding genes continues to be enigmatic. figuring out this recruitment is clinically major simply because off-target relief job at oncogenes may end up in chromosomal translocations and tumorigenesis ...
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The majority of modern clinical tests assay for just one analyte at a time [18]. They determine the presence or absence of the analyte, and sometimes its quantity, but provide no information about other analytes. For example, a nucleic acid test for HIV-1 determines whether or not HIV-1 RNA is present in blood, and how much, but provides no information about, for example, the presence of antibodies to CMV. Although such tests are the mainstay of modern medicine, conceptually, they are limited to providing a "20 questions," yes-or-no approach to diagnosis.. The major exception is the standard culture-based method for diagnosing bacterial infections. In this method, the first step is to apply a clinical sample to standard culture media to see what grows [19]. This method is powerful in that it presupposes little about the identity of the bacteria: it can distinguish among many bacteria with a single test, and often reveals the presence of species that were clinically unexpected. Conceptually, this ...
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Creative Biostructure develops comprehensive protein evolution and engineering platform to generate gene diversification by site-directed mutagenesis libraries.
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This study investigated whether fingolimod reduced newly produced T and B lymphocytes and T-cell receptor repertoire diversity in peripheral blood in patients
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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. ...
article{703bd660-903e-43ef-94d0-d5a95efca667, abstract = {,p,Data that defines IGHV (immunoglobulin heavy chain variable) germline gene inference using sequences of IgM-encoding transcriptomes obtained by Illumina MiSeq sequencing technology are described. Such inference is used to establish personalized germline gene sets for in-depth antibody repertoire studies and to detect new antibody germline genes from widely available immunoglobulin-encoding transcriptome data sets. Specifically, the data has been used to validate (Parallel antibody germline gene and haplotype analyses support the validity of immunoglobulin germline gene inference and discovery (DOI: 10.1016/j.molimm.2017.03.012) (Kirik et al., 2017) [1]) the inference process. This was accomplished based on analysis of the inferred germline genes association to the donors different haplotypes as defined by their different, expressed IGHJ alleles and/or IGHD genes/alleles. The data is important for development of validated germline ...
The indigenous intestinal microbiota is frequently considered an additional major organ of the human body and exerts profound immunomodulating activities. Germ-free (GF) mice display a significantly different inflammatory responsiveness pattern compared with conventional (CV) mice, and this was dubbed a "hyporesponsive phenotype." Taking into account that the deposition of immune complexes is a major event in acute inflammation and that GF mice have a distinct Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig repertoire interferes with the inflammatory responsiveness of GF mice. We found that serum transfer from CV naive mice was capable of reversing the inflammatory hyporesponsiveness of GF mice in sterile inflammatory injury induced by intestinal ischemia and reperfusion, as well as in a model of lung infection by Klebsiella pneumoniae. Transferring serum from Ig-deficient mice to GF animals did not alter their response to inflammatory insult; however, injecting ...
Dr. Victor Greiff received his PhD in Theoretical Immunology from the Humboldt University of Berlin (Germany, 2012) where he had studied the specificity of antibody repertoires using high-throughput antibody-binding proteomics data and mathematical modeling. In 2013, he joined the Laboratory for Systems and Synthetic Immunology (Prof. Sai T. Reddy) located at ETH Zürich where his main focus lies on gaining a systems view of antibody repertoire complexity by coupling large-scale immunogenomics data to computational immunology ...
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Gene conversion-like events between rearranged IGHV3-23*01 gene sequences and germline VH sequences superimposed by somatic hypermutation (SHM). IGHV3-23*01 mut
Deoxyuridine (dU) is a pyrimidine deoxyribonucleoside, and a derivative of the nucleoside uridine, with the only difference being that, in dU, a hydrogen (-H) group is substituted for uridine s OH group located at the 2 -position of the ribose. dU is generated in cellular DNA as a deamination product of dC (deoxycytidine), with the deamination process catalyzed by the enzyme AID (activation-induced cytidine deaminase) (1). AID is a B cell-specific gene that is necessary for antibody gene diversification via class-switch recombination and somatic hypermutation (2, 3). The dC-to-dU conversion(s) by AID occurs in the IgG locus, with various gene diversification pathways arising from the different DNA repair mechanisms used by B-cells to repair the dU lesion (1).. dC-to-dU conversion via cytidine deamination is also implicated in innate immunity to retroviruses. Here deamination of dC is mediated by the enzyme APOBEC3G, which is present in T cells, acting on the first (minus) strand cDNA of ...
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Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase | Adenosine Kinase...Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase | Adenosine Kinase...

Intro In humans and mice, main antibody (Ig) diversity is produced by V(D)J recombination, which is dependent within the RAG-1 ... Author Summary To generate highly specific antibodies in response to an immune challenge, the antibody genes in triggered B ... Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase. Posted on July 16, 2017. ... AID induces point mutation of antibody V genes in all vertebrates, as well as transfer of short sequences from nonfunctional ...
more infohttp://cutelevision.org/affinity-maturation-and-class-switching-of-antibodies-requires-activation-induced-cytidine-deaminase/

A large semi-synthetic single-chain Fv phage display library based on chicken immunoglobulin genes | BMC Biotechnology | Full...A large semi-synthetic single-chain Fv phage display library based on chicken immunoglobulin genes | BMC Biotechnology | Full...

Because of the way in which gene conversion introduces diversity, the naïve antibody repertoire of the chicken can easily be ... Virus antibodies were detected in a competitive ELISA. The chicken-derived phage library described here is expected to be a ... Most existing antibody repertoires are derived from human immunoglobulin genes. Genes from other species can, however, also be ... Single chain antibody fragments that recognise haptens, proteins and virus particles were selected from this repertoire. ...
more infohttps://bmcbiotechnol.biomedcentral.com/articles/10.1186/1472-6750-4-6

Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Original View Point		Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Original View Point

... certain positions can be randomized at a defined diversity to improve the affinity. It is able to create any sub-libraries to ... Phage Display Antibody Library Screening Subsequent library screening will fish out the antibody mutants that have high ... To further improve antibody affinity maturation, Creative Biolabs successfully updated its unique antibody affinity maturation ... If the structure of the antibody/antigen complex is available or modeling the structure of the antibody/antigen is possible, ...
more infohttp://www.originalviewpoint.com/story/139023/creative-biolabs-made-breakthroughs-in-improving-antibody-affinity-maturation.html

Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | North Dakota Magazine		Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | North Dakota Magazine

... certain positions can be randomized at a defined diversity to improve the affinity. It is able to create any sub-libraries to ... Phage Display Antibody Library Screening Subsequent library screening will fish out the antibody mutants that have high ... To further improve antibody affinity maturation, Creative Biolabs successfully updated its unique antibody affinity maturation ... If the structure of the antibody/antigen complex is available or modeling the structure of the antibody/antigen is possible, ...
more infohttp://www.northdakota-magazine.com/story/151139/creative-biolabs-made-breakthroughs-in-improving-antibody-affinity-maturation.html

Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Delaware News Reporter		Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Delaware News Reporter

... certain positions can be randomized at a defined diversity to improve the affinity. It is able to create any sub-libraries to ... Phage Display Antibody Library Screening Subsequent library screening will fish out the antibody mutants that have high ... To further improve antibody affinity maturation, Creative Biolabs successfully updated its unique antibody affinity maturation ... If the structure of the antibody/antigen complex is available or modeling the structure of the antibody/antigen is possible, ...
more infohttp://www.delawarenewsreporter.com/story/133609/creative-biolabs-made-breakthroughs-in-improving-antibody-affinity-maturation.html

Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Oregon News Headlines		Creative Biolabs Made Breakthroughs in Improving Antibody Affinity Maturation | Oregon News Headlines

... certain positions can be randomized at a defined diversity to improve the affinity. It is able to create any sub-libraries to ... Phage Display Antibody Library Screening Subsequent library screening will fish out the antibody mutants that have high ... To further improve antibody affinity maturation, Creative Biolabs successfully updated its unique antibody affinity maturation ... If the structure of the antibody/antigen complex is available or modeling the structure of the antibody/antigen is possible, ...
more infohttp://www.oregonnewsheadlines.com/story/144693/creative-biolabs-made-breakthroughs-in-improving-antibody-affinity-maturation.html

Genetic basis of antibody diversity | The Lasker FoundationGenetic basis of antibody diversity | The Lasker Foundation

... showing that rearrangements of genes lead to an infinite diversity of antibodies. ... Leder, for his studies of the genetics of antibody diversity, which led to his profound discovery that cancer can result from a ... Tonegawa, for proving brilliantly that antibody diversity is the result of an ordered system of gene rearrangement, and for ... Tonegawa determined the genetic mechanism of antibody diversity and showed that new genes are created through rearrangement of ...
more infohttp://www.laskerfoundation.org/awards/show/genetic-basis-of-antibody-diversity/

A Developmental Approach to the Biological Basis for Antibody Diversity | SpringerLinkA Developmental Approach to the Biological Basis for Antibody Diversity | SpringerLink

The emphasis in this discussion will be on early events in differentiation of antibody-producing cells, an area of immunology ... Mechanism of antibody diversity: Germ line basis for variability. Science 168: 325.PubMedCrossRefGoogle Scholar ... Medullary Cell Plasma Cell Differentiation Antibody Diversity Peripheral Lymphoid Tissue Single Stem Cell These keywords were ... Cooper M.D., Lawton A.R., Kincade P.W. (1972) A Developmental Approach to the Biological Basis for Antibody Diversity. In: ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4684-3042-4_2

The Generation of Antibody Diversity - Molecular Biology of the Cell - NCBI BookshelfThe Generation of Antibody Diversity - Molecular Biology of the Cell - NCBI Bookshelf

... a human can probably make more than 1012 different antibody molecules-its preimmune antibody repertoire. Moreover, the antigen- ... After repeated stimulation by antigen, B cells can make antibodies that bind their antigen with much higher affinity-a process ... Thus, antigen stimulation greatly increases the antibody arsenal. ... making the antibody defense force even more formidable. The ... binding sites of many antibodies can cross-react with a variety of related but different antigenic determinants, ...
more infohttps://www.ncbi.nlm.nih.gov/books/NBK26860/

Antibody Diversity Mechanism Essay - 1223 Words - AvroArrowAntibody Diversity Mechanism Essay - 1223 Words - AvroArrow

Free essay on Antibody Diversity Mechanism. A transposition- like mechanism can be used for other types of DNA rearrangement ... Antibody Diversity Mechanism Essay. 1223 words - 5 pages A transposition- like mechanism can be used for other types of DNA ... Other Papers Like Antibody Diversity Mechanism. Holidays In Albania Essay. 1636 words - 7 pages Have you ever thought about ... Antibody diversity is generated by the rearrangement of variable region gene segments during the ...view middle of the document ...
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PPT - Generation of Antibody Diversity PowerPoint Presentation - ID:6869117PPT - Generation of Antibody Diversity PowerPoint Presentation - ID:6869117

The big question:how do you get all those different antibodies? Two other big questions- getting different classes with the ... 1 antibody structure role of antibody in defence polyclonal antibodies monoclonal antibodies. 1 revision antibody structure ( ... diversity relationship of diversity & stability diversity index microclimates using quadrants. diversity. diversity is all ... lab 6. antibody detection. the test used to detect antibodies is called an antibody screen antibody screens are used for: ...
more infohttps://www.slideserve.com/amal-herring/generation-of-antibody-diversity

Study Adds to Our Understanding of Antibody Diversity - Healthcanal.com : Healthcanal.comStudy Adds to Our Understanding of Antibody Diversity - Healthcanal.com : Healthcanal.com

Each new B cell makes its own unique antibody by mixing and matching from a set of a few hundred genes, taking one each from ... Each new B cell makes its own unique antibody by mixing and matching from a set of a few hundred genes, taking one each from ... "We were surprised and excited to find that B cell survival could be influenced by a non-antigen-binding region of the antibody ... "We were surprised and excited to find that B cell survival could be influenced by a non-antigen-binding region of the antibody ...
more infohttps://www.healthcanal.com/immune-system/52014-study-adds-to-our-understanding-of-antibody-diversity.html

Antibody Immunoglobulin DiversityAntibody Immunoglobulin Diversity

Due to diversity in microbes, the antibody needs to adopt variations to allow their interactions with many different antigens. ... All microbes trigger an antibody response. Due to diversity in microbes, the antibody needs to adopt variations to allow their ... Antibody Immunoglobulin Diversity. News-Medical. https://www.news-medical.net/health/Antibody-Immunoglobulin-Diversity.aspx. ( ... The locus for antibodies is a relatively large segment. There are several distinct genes for each domain of the antibody. There ...
more infohttps://www.news-medical.net/health/Antibody-Immunoglobulin-Diversity.aspx

Combinatorial events in generation of antibody diversity. - Semantic ScholarCombinatorial events in generation of antibody diversity. - Semantic Scholar

As joining of these elements is imprecise and is occurring with nucleotide additions or deletions, the created diversity is in ... Consequently, these processes not only develop the antibody repertoire but also solve some other problems of the adaptive ... Due to somatic hypermutation, the affinity of synthesized antibody increases even more. Another variant of combinatorial ... genes and the formation of various immunoglobulin isotypes with different effector functions but with the same antibody ...
more infohttps://www.semanticscholar.org/paper/Combinatorial-events-in-generation-of-antibody-div-Nezlin/35a0e0d058763f75faa11b232a5d8ef58cb0a6ff

Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. - Radcliffe Department of MedicineContribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. - Radcliffe Department of Medicine

Animals, Antibody Diversity, Base Sequence, Binding Sites, Antibody, Genes, Humans, Immunoglobulin Heavy Chains, Immunoglobulin ... Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. Rabbitts TH., Matthyssens G., Hamlyn PH ...
more infohttps://www.rdm.ox.ac.uk/publications/601749

Surprising Diversity of Antibody Family Provides Clues for HIV Vaccine Design | Infection Control TodaySurprising Diversity of Antibody Family Provides Clues for HIV Vaccine Design | Infection Control Today

... have described how a single family of antibodies that broadly neutralizes different strains of HIV has evolved remarkably ... Surprising Diversity of Antibody Family Provides Clues for HIV Vaccine Design. Sep 25, 2014 ... It starts producing antibodies that can grab or at least block the viruss most vulnerable sites-sites that dont change much ... "In a sense, this antibody family takes more than one shot on goal in order to hit divergent forms of HIV," says Ian A. Wilson, ...
more infohttp://www.infectioncontroltoday.com/vaccines-vaccination/surprising-diversity-antibody-family-provides-clues-hiv-vaccine-design

Numerous antibodies can be prepared, against one antigen, each binds to unique epitopes. How is this antibody diversity...Numerous antibodies can be prepared, against one antigen, each binds to unique epitopes. How is this antibody diversity...

Antibody proteins can physically change their shape to bind different epitopes ... How is this antibody diversity generated?. This is a Most important question of gk exam. Question is : Numerous antibodies can ... Numerous antibodies can be prepared, against one antigen, each binds to unique epitopes. How is this antibody diversity ... Title: Numerous antibodies can be prepared, against one antigen, each binds to unique epitopes. How is this antibody diversity ...
more infohttps://mympsc.com/Share.aspx?ArticleID=D307325C-8CE3-41D5-868F-03896358A756

Limiting CDR-H3 Diversity Abrogates the Antibody Response to the Bacterial Polysaccharide α 1→3 Dextran | The Journal of...Limiting CDR-H3 Diversity Abrogates the Antibody Response to the Bacterial Polysaccharide α 1→3 Dextran | The Journal of...

Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity 13: 37-45. ... Limiting CDR-H3 Diversity Abrogates the Antibody Response to the Bacterial Polysaccharide α 1→3 Dextran. Tamer I. Mahmoud, ... Analysis of the diversity of murine antibodies to dextran B1355. III. Idiotypic and spectrotypic correlations. Eur. J. Immunol. ... Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice ...
more infohttp://www.jimmunol.org/content/187/2/879

MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines | Science...MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines | Science...

Antibody avidities can also be determined by the ratio of antibody on and off rates as determined by SPR. Antibody on rates ... MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines ... MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines ... MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines ...
more infohttps://stm.sciencemag.org/content/3/85/85ra48?ijkey=484ea1b72a9c1a8b05fccbecc7a09a3d6c07b7a6&keytype2=tf_ipsecsha

May 1982 - Scientific AmericanMay 1982 - Scientific American

The Genetics of Antibody Diversity. Segments of DNA and RNA are shuffled and joined in various ways as cells of the immune ...
more infohttps://www.scientificamerican.com/magazine/sa/1982/05-01/

nature.com searchnature.com search

Rights & permissionsfor article Genes of lymphocytes I: Diverse means to antibody diversity . Opens in a new window. ... Rights & permissionsfor article Gene rearrangement and the generation of diversity . Opens in a new window. ... Rights & permissionsfor article Lymphocyte differentiation: Control of antibody production . Opens in a new window. ... Rights & permissionsfor article Antibodies, introns and biosynthetic versatility . Opens in a new window. ...
more infohttps://www.nature.com/search?author=%22Miranda%20Robertson%22&error=cookies_not_supported&code=bc827403-2f85-449c-9873-9d9e7a76b5f4

CiteSeerX - How the immune system generates diversity: Pathogen space coverage with random and evolved antibody librariesCiteSeerX - How the immune system generates diversity: Pathogen space coverage with random and evolved antibody libraries

Here we address the contribution of antibody gene libraries to the antibody repertoire. We introduce a general framework, in ... For the antibody/pathogen matching rules that we studied, the scaling relation between fitness and the size of the evolved ... We discuss how our results compare to the antibodies that are expressed in newborns, and we discuss the implications of our ... We use the genetic algorithm as a model of evolution to investigate the type of antibody repertoires that might evolve in ...
more infohttp://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.36.9580

Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine...Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine...

60 APPLIED LIFE SCIENCES; HIV; peptide microarray; diversity; antibody; vaccine. OSTI Identifier:. 1201749. ... Title: Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 ... Accepted Manuscript: Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for ... The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of ...
more infohttps://www.osti.gov/pages/biblio/1201749-quantification-epitope-diversity-hiv-specific-binding-antibodies-peptide-microarrays-global-hiv-vaccine-development

life of pi (Example) - MindMeisterlife of pi (Example) - MindMeister

9.6.2. + B Cells and Antibodies. 9.6.3. + The Generation of Antibody Diversity. 9.6.4. + T Cells and MHC Proteins. 9.6.5. + ... 6.1.2. + The Diversity of Genomes and the Tree of Life. 6.1.3. + Genetic Information in Eucaryotes. 6.1.4. + References. 6.2. ... 10.4.1. + The Molecular Mechanisms of Membrane Transport and the Maintenance of Compartmental Diversity. 10.4.1.1. # There Are ...
more infohttps://www.mindmeister.com/51222573/alberts-molecular-cell-biology-major-headings
  • The first direct evidence that DNA is rearranged during B cell development came in the 1970s from experiments in which molecular biologists compared DNA from early mouse embryos, which do not make antibodies, with the DNA of a mouse B cell tumor, which makes a single species of antibody molecule . (nih.gov)
  • Jawed fish appear to be the most primitive animals that are able to make antibodies like those described for mammals. (wikipedia.org)
  • Since each of the antibodies are different for each of the antigens, the body needs to be capable for generating these proteins. (news-medical.net)
  • Antibody proteins can physically change their shape to bind different epitopes, 5. (mympsc.com)
  • During humoral immune responses, proteins called antibodies, which can bind to and destroy pathogens, are secreted into the blood and other body fluids. (encyclopedia.com)
  • This technology was further developed and improved by groups at the Laboratory of Molecular Biology with Greg Winter and John McCafferty, The Scripps Research Institute with Lerner and Barbas and the German Cancer Research Center with Breitling and Dübel for display of proteins such as antibodies for therapeutic protein engineering. (wikipedia.org)
  • Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines. (sciencemag.org)
  • Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. (osti.gov)
  • The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. (osti.gov)
  • This review discusses the importance of HLA in the clinical setting in South Africans and highlights how tools such as HLA imputation might augment standard HLA typing methods to increase our understanding of HLA diversity in our populations, which will better inform disease association studies, donor recruitment strategies into bone marrow registries and our understanding of human genetic diversity in South Africa. (who.int)
  • This showed that the DNA sequences encoding an antibody molecule are rearranged at some stage in B cell development ( Figure 24-36 ). (nih.gov)
  • MF59 shifted the focus of antibody responses from predominantly HA2 sequences (conserved between H5 and seasonal H1 strains) to sequences in HA1 [receptor binding domain (RBD)] and NA (sialic acid-binding site). (sciencemag.org)
  • Here, we describe multiple studies to evaluate the effects of MF59 on the antibody responses induced by swine-origin influenza virus (SOIV) H1N1 and H5N1 vaccines in various age groups. (sciencemag.org)
  • In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. (cdc.gov)
  • The findings give us new options for vaccine design," adds TSRI professor Dennis R. Burton, who directs the International AIDS Vaccine Initiative's (IAVI) Neutralizing Antibody Consortium and the National Institutes of Health-sponsored Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI. (infectioncontroltoday.com)
  • The new research, reported in the September 25, 2014 issue of the journal Cell, is part of a broad effort to "retro design" an effective HIV vaccine, based on an understanding of rare, natural antibodies that effectively hit HIV's most vulnerable sites. (infectioncontroltoday.com)
  • But many researchers now are convinced that these antibodies hold the key to a successful preventive vaccine. (infectioncontroltoday.com)
  • The big challenge remains the "retro design": taking information about antibodies such as PGT121 and using it to design the main vaccine ingredient-the immunogen molecule-that can elicit high levels of the same antibodies in people. (infectioncontroltoday.com)
  • Antibody affinity, as inferred by greatly diminished (≥10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. (sciencemag.org)
  • The scaffold antibody gene one of the libraries, the M:anti-pep library, was chosen based on hypervariable loop canonical structures that are characteristic of other anti-peptide antibodies. (utexas.edu)
  • Additionally, all of the contact residues of this antibody are commonly used contact residues in other anti-peptide antibodies. (utexas.edu)
  • These positions and others were varied to incorporate the natural diversity of other anti-peptide antibodies. (utexas.edu)
  • Positions were chosen for variation based on their usage as contact residues in both anti-peptide and anti-protein antibodies. (utexas.edu)
  • The diversity generated by this mechanism is occurring in the third hypervariable region thus directly affecting combining site of the antibody. (avroarrow.org)
  • The M:anti-pep library yielded specific antibodies to both peptides with dissociation constants as low as 14 nM against AT and 18 nM against NPY. (utexas.edu)
  • Active vaccination to elicit a long-term protective response is far more feasible as a public health strategy than infusions of expensive antibodies would be. (infectioncontroltoday.com)
  • Combinations of the selected consensus mutations from these libraries provide moderate enhancements to the kinetics and expression of the wild-type antibody in a non-synergistic manner. (utexas.edu)
  • For the antibody/pathogen matching rules that we studied, the scaling relation between fitness and the size of the evolved antibody library is only a shifted variant of the scaling relation that we obtain with random libraries of the same size. (psu.edu)
  • Both of these strategies used to create these antigen-class focused libraries used a single scaffold antibody gene that contained diversity only in the variable heavy region. (utexas.edu)
  • Extremely high rates of mutagenesis (2.2% of the gene to 2.7%) were used to create two libraries of the anti-digoxin antibody 26-10. (utexas.edu)
  • The libraries had been screened by others in an attempt to examine the effects of highrates of mutagenesis on the directed evolution of an antibody. (utexas.edu)
  • This study confirmed that high-error rate antibody libraries contain more active clones than expected. (utexas.edu)
  • Overall picture- diversity produced by combining a number of variable regions with at least one joining region, plus the constant regions. (slideserve.com)