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.
Immunoglobulin Light Chains
Somatic Hypermutation, Immunoglobulin
Binding Sites, Antibody
Immunoglobulin Heavy Chains
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).
Amino Acid Sequence
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).
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.
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.
Sequence Analysis, DNA
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).
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.
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.
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 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.
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)
PPT - Generation of Antibody Diversity PowerPoint Presentation - ID:6869117
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 events in generation of antibody diversity. - Semantic Scholar
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
Generation of B-cell / antibody diversity | British Society for Immunology
One of the major roles that B cells play in an immune response is the production of antibodies, that specifically recognise and bind to proteins on the invading bacteria or virus particles. The binding of specific antibody to its target can prevent viruses from entering cells or aid phagocytes in identifying and destroying the bacteria or viruses.
Newly B-cell Selection Process Aids the Understanding of Antibody Diversity
B cells, the elite soldiers of the bodys immune system serve as an army that is ready to recognize and destroy the invading antigens
Antibody repertoire | Article about Antibody repertoire by The Free Dictionary
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
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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 ...
Somatic Diversification of Immunoglobulin Genes in Galt - Katherine Knight
The intestinal commensal microbiota is required for development of lymphoid tissues and mucosal immunity in vertebrates. However, little is known of the mechani...
somatic diversification of immunoglobulins involved in immune response Gene Ontology Term (GO:0002208)
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
Sheepish B cells: evidence for antigen-independent antibody diversification in humans and mice | JEM
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 ...
Study Adds to Our Understanding of Antibody Diversity - Healthcanal.com : Healthcanal.com
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 ...
Genetic basis of antibody diversity | The Lasker Foundation
For his imaginative studies of somatic recombination in the immune system, showing that rearrangements of genes lead to an infinite diversity of antibodies.
The V(H) and C(H) immunoglobulin genes of swine: Implications for repertoire development<...
TY - JOUR. T1 - The V(H) and C(H) immunoglobulin genes of swine. T2 - Implications for repertoire development. AU - Butler, J. E.. AU - Sun, J.. AU - Kacskovics, I.. AU - Brown, W. R.. AU - Navarro, P.. PY - 1996/11/1. Y1 - 1996/11/1. N2 - Swine have the largest number of IgG subclass genes of all species so far studied but have a single gene for IgA which occurs in two allelic forms that differ in hinge length. Swine also have constant region genes for Cμ and Cε, but lack a gene homologous to that which encodes IgD in rodents and primates, despite the otherwise high degree of sequence similarity of all other swine C (H) genes with those of humans. Swine have , 20 V(H) genes, a single J(H) and perhaps a limited number of D(H) segments. Newborn piglets show preferential V(H) and D(H) usage and may use gene conversion as a mechanism for expanding their antibody repertoire. Despite the close similarity of their Ig gene sequences to humans, swine belong to the group of animals that includes ...
Germline VH/VL pairing in antibodies. - Semantic Scholar
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.
Functional and pseudogenes are similarly organized and may equ...
Functional and pseudogenes are similarly organized and may equally contribute to the extensive antibody diversity of the IgVHII family.: Eleven germ-line immuno
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High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular info about humoral | kinase inhibitor...
High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular info about humoral immunity. with antibody frequencies and somatic hypermutation to create a logistic regression model for prediction from the immunological position of clones. The model could predict clonal position with high self-confidence but only once using MAF mistake and bias PPP3CC corrected Ig-seq data. Improved accuracy by MAF supplies the potential to upfront Ig-seq and its own utility in immunology and biotechnology greatly. did not possess a precise match in the primer collection but had been still well displayed in the info set due Evacetrapib to a higher level of mispriming, suggesting that reduced primer sets may be designed that allow mismatches toward the 5 end of primers. These findings also demonstrate the need to exclude primer binding regions from full-VDJ diversity analysis, as was done throughout this study. We also investigated the role of V-geneCspecific primer annealing temperature ...
Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells | Blood | American Society of Hematology
Abstract. The adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient diversity to recognize
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BME/CIC Special Seminar - Sai Reddy, PhD, Associate Professor, ETH-Zurich: Encoding and decoding specificity in antibody repertoires by deep learning ...
Antibody Repertoire Development in Fetal and Neonatal Piglets. XX. B Cell Lymphogenesis Is Absent in the Ileal Peyers Patches,...
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 ...
Immunology | Journal of Clinical Pathology
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 ...
Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting | Science Advances
RNA spike-in standards are becoming an essential tool to assess errors and bias in sequencing data, the most notable example being the establishment of the External RNA Controls Consortium (ERCC) spike-in mix (36). We translated this concept to Ig-seq by designing a set of synthetic (in vitro transcribed) RNA standards. It is impractical to generate a spike-in mix comprising the full diversity of antibody repertoires at a clonal or V-gene level (,140 V-genes in IGHV repertoire of BALB/c mice). However, fractional sample spike-ins, like the ERCC spike-in mix (92 polyadenlyated transcripts), have proven to be valuable and sufficient for evaluation of errors and bias in sequencing data. We designed our synthetic spike-ins to consist of 16 full-length antibody sequences on the basis of mouse VH regions. Notable spike-in features were the incorporation of 16 unique CDR3 amino acid sequences, seven different V-genes, designed positions for somatic hypermutation, a synthetic segment [for bioinformatic ...
Human antibody repertoire after VSV-Ebola vaccination identifies novel targets and virus-neutralizing IgM antibodies
Development of an effective vaccine against Ebola virus is of high priority. However, knowledge about potential correlates of protection and the durability of immune response after vaccination is limited. Here, we elucidate the human antibody repertoire after administration of vesicular stomatitis v …
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FYI: Ticking time-bomb fault will brick Cisco gear after 18 months • The Register
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Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire<...
TY - JOUR. T1 - Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire. AU - Chang, Sooghee. AU - Yang, Liu. AU - Moon, Young Mee. AU - Cho, Young Gyu. AU - Min, So Youn. AU - Kim, Tae Joo. AU - Kim, Young Joo. AU - Patrick, Wilson. AU - Kim, Ho Youn. AU - Mohan, Chandra. PY - 2009/10. Y1 - 2009/10. N2 - When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited three sequence motifs in their immunoglobulin heavy chains, including increased cationicity in CDR3 (motif A), reduced anionicity in CDR2 (motif B) and increased aspartate at H50 (motif C). The present study was designed to elucidate the extent to which these ANA-associated sequence motifs might be hard-wired into the primary B-cell repertoire in lupus. The immunoglobulin heavy chain sequence of total splenic B-cells, follicular B-cells and marginal zone B-cells from B6.Sle1 congenic mice and ...
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Early restriction of the human antibody repertoire | Science
Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (VH) of mouse antibodies is also developmentally ordered: the number of VH gene segments rearranged in B lymphocytes of fetal mice is small but increased progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of VH gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human VH element proved to be closely related to the VH element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence. ...
Manser, Timothy L. - Philadelphia University + Thomas Jefferson University - Thomas Jefferson University
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 ...
Georges J. F. Köhler - Wikipedia
In April 1974 Köhler took up a post-doctoral research fellowship at the Laboratory of Molecular Biology in Cambridge, UK where he began working with César 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 collaboration on the technique when he returned to Basel Institute of Immunology in April 1974. Köhler remained at the Basel Institute for another nine years, during which time he continued investigating antibody diversity and in the early 1980s began working on the development of transgenic mice as a tool to understand the mechanism that underlies self-tolerance. In 1986 Köhler became director of the Max Planck Institute of Immunobiology where he worked until his death in 1995.. ...
Cancer Seminar | MDC Berlin
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))
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Does activation-induced deaminase initiate antibody diversification by by Janet Stavnezer and Sean P. Bradley
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.
Eleven distinct VH gene families and additional patterns of sequence variation suggest a high degree of immunoglobulin gene...
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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Team:Peking University/Project - 2008.igem.org
However, we overlooked a mechanism natural has adopted for rapid evolution of proteins: adaptive immunity that generates a huge pool of antibodies.It is well-known that B-cells are capable of producing a large pool of new antibodies upon antigen stimuli, which is a most important protective mechanism for animals. People have been curious about the molecular mechanism of antibody generation. Recent works have revealed that an enzyme: Activation-Induced (Cytidine) Deaminase (AID) serves as an essential protein in three processes for antibody diversity, namely somatic hypermutation (SHM), class switch recombination (CSR) and gene conversion. Briefly speaking, AID converts cytidine to uracil by oxidizing the amino group to carbonyl group, resulting in mismatch of Watson-Crick base pair. Then DNA lesion repair pathways (base excision repair, BER; mismatch repair, MMR)are employed to bring DNA back to normal. In this process, the coding sequence for the hypervariable region of immunoglobulin is ...
Stability engineering of the human antibody repertoire | Garvan Institute of Medical Research
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.
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B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation | Genome...
A diverse B-cell repertoire is essential for recognition and response to infectious and vaccine antigens. High-throughput sequencing of B-cell receptor (BCR) genes can now be used to study the B-cell repertoire at great depth and may shed more light on B-cell responses than conventional immunological methods. Here, we use high-throughput BCR sequencing to provide novel insight into B-cell dynamics following a primary course of hepatitis B vaccination. Nine vaccine-naïve participants were administered three doses of hepatitis B vaccine (months 0, 1, and 2 or 7). High-throughput Illumina sequencing of the total BCR repertoire was combined with targeted sequencing of sorted vaccine antigen-enriched B cells to analyze the longitudinal response of both the total and vaccine-specific repertoire after each vaccine. ELISpot was used to determine vaccine-specific cell numbers following each vaccine. Deconvoluting the vaccine-specific from total BCR repertoire showed that vaccine-specific sequence clusters
Frontiers | High-throughput sequencing of the expressed torafugu (Takifugu rubripes) antibody sequences distinguishes IgM and...
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
Department of Entomology: Faculty
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 ...
Ollivier Hyrien, PhD
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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Pregnancy and addictions : conseils pour les parents | Fondation Mustela
On average, a quarter of women are smokers during early pregnancy and one in twenty suffers from alcoholism. This is due in part to lack of knowledge about the harmful effects of maternal addictions on the fetus, but also a lack of familiarity with options available, such as the use of replacement products. SIX KEY IDEAS IN THE
Publications | SBRC
De Genst, E., K. Silence, M. Arbabi Ghahroudi, K. Decanniere, R. Loris, J. Kinne, L. Wyns, and S. Muyldermans, Strong in vivo maturation compensates for structurally restricted H3 loops in antibody repertoires., J Biol Chem, vol. 280, issue 14, pp. 14114-21, 2005 Apr 8. ...
Dr. Rudra Narayan Biswal, General Medicine Doctor / Internal Medicine Doctor, Cuttack, Odisha
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"Tracking Antibody Diversity". NIH Director's Early Independence Award Highlights. National Institutes of Health. Retrieved 2017 ... Award for his work using two-photon microscopy to understand the changes over time of the level of diversity of antibodies in ...
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 ... an antibody lacking light chains, and can be used to produce single-domain antibodies, which are essentially the variable ... an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications". Antibody ... The resulting antibody, IgM, is secreted as a tetramer in teleost fish instead of the typical pentamer found in mammals and ...
June 2013). "Reshaping antibody diversity". Cell. 153 (6): 1379-93. doi:10.1016/j.cell.2013.04.049. PMC 4007204. PMID 23746848 ... de los Rios M, Criscitiello MF, Smider VV (August 2015). "Structural and genetic diversity in antibody repertoires from diverse ... It is a small region at the tip of the antibody's antigen-binding fragment and contains parts of the antibody's heavy and light ... Each arm of the Y-shaped antibody has an identical paratope at the end. Paratopes make up the parts of the B-cell receptor that ...
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. ...
Generation of the TCR diversity. The generation of TCR diversity is similar to that for antibodies and B cell antigen ... The recombination process that creates diversity in BCR (antibodies) and TCR is unique to lymphocytes (T and B cells) during ... the family is named after antibodies (also called immunoglobulins). The TCR is similar to a half-antibody consisting of a ... Whereas the antibody uses its Fc region to bind to Fc Receptors on leukocytes, TCR is already docked onto the cell membrane. ...
Williamson, A. R. (1972). "Extent and control of antibody diversity". The Biochemical Journal. 130 (2): 325-33. doi:10.1042/ ...
Tanford, Charles (1968). "Chemical basis for antibody diversity and specificity". Accounts of Chemical Research. 1 (6): 161-167 ... 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 R, Edelmann W, Scharff MD, Roa S (August 2012). "AIDing antibody diversity by error-prone mismatch repair". Seminars in ... where POLH is used to introduce genetic variation into antibody genes. However, this error-prone MMR pathway may be triggered ...
Normally, the Y-shaped antibody molecules consist of two heavy (or long) chains along the length of the Y, and two light (or ... Chuluunbat, B.; Charruau, P.; Silbermayr, K.; Khorloojav, T.; Burger, P. A. (2014). "Genetic diversity and population structure ... These "heavy-chain-only" antibodies, discovered in 1993, are thought to have developed 50 million years ago, after camelids ... Fedewa, Jennifer L. (2000). "Camelus bactrianus". Animal Diversity Web. University of Michigan Museum of Zoology. Archived from ...
"Commonality despite exceptional diversity in the baseline human antibody repertoire". Nature. 566 (7744): 393-397. Bibcode: ... This database serves as a resource for data on antibody and T cell epitopes studied in humans, non-human primates, and other ... This immunome data can also be helpful when testing antibody therapies on non-human primates to ensure they are safe for humans ... convergence and loci diversity". Immunogenetics. 56 (11): 818-832. doi:10.1007/s00251-004-0751-5. PMID 15654599. Wooden, SL; ...
Avian immune system
Such antibodies are found within the egg when it is laid and originated from the yolk of the egg. Kramer and Cho have shown ... This results in a low diversity from gene rearrangements of Ig heavy and light chains. However, clusters of pseudogenes ... Using monoclonal antibodies that are specific for chicken T cell surface antigens, the development of T cells in birds is ... Upon hatch, birds do not have a library of genetic information for B cells to use for antibody production. Instead, B cells ...
Liu, Y. C.; Milgroom, M. G. (2007). "High diversity of vegetative compatibility types in Cryphonectria parasitica in Japan and ... "Isolation of a novel mycovirus OMIV in Pleurotus ostreatus and its detection using a triple antibody sandwich-ELISA". Journal ... Araújo, A., Jansen, A. M., Bouchet, F., Reinhard, K., Ferreira, L. F. (2003). Parasitism, the Diversity of Life, and ...
Human genome - Simple English Wikipedia, the free encyclopedia
2000). "Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity". Cell. 101 (6): 671-684. ... Mathial Uhlen and Fredrik Ponten (2005). "Antibody-based proteomics for human tissue profiling". Mollecular & Cellular ...
"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 " ...
TEs may also have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J ... "The B73 maize genome: complexity, diversity, and dynamics". Science. 326 (5956): 1112-5. Bibcode:2009Sci...326.1112S. doi ...
Antibody types. The antibodies used for specific detection can be polyclonal or monoclonal. Polyclonal antibodies are ... The diversity of IHC markers used in diagnostic surgical pathology is substantial. Many clinical laboratories in tertiary ... Thus, polyclonal antibodies are a heterogeneous mix of antibodies that recognize several epitopes. Monoclonal antibodies are ... while secondary antibodies are raised against immunoglobulins of the primary antibody species. The secondary antibody is ...
List of University of California, San Diego people
Nobel Prize recipient for physiology or medicine for his work on antibody diversity. Craig Venter, BA (Biochemistry), 1972; PhD ...
Aust G, Wandel E, Boltze C, Sittig D, Schütz A, Horn LC, Wobus M (Apr 2006). "Diversity of CD97 in smooth muscle cells". Cell ... antibody treatment but not gene targeting curtails granulocyte migration". Journal of Immunology. 181 (9): 6574-83. doi:10.4049 ... CD97 antibodies and lack of CD97 or CD55 in mice reduced synovial inflammation and joint damage in collagen- and K/BxN serum ... "CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism". ...
List of Nobel laureates in Physiology or Medicine
"for his discovery of the genetic principle for generation of antibody diversity" . ... in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies" [83 ...
A capsule-specific antibody may be required for phagocytosis to occur. Capsules also contain water which protects the bacteria ... DiversityEdit. The capsule is found most commonly among gram-negative bacteria: *Escherichia coli (in some strains) ...
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 ...
Adaptive immune system
Immunological diversityEdit. An antibody is made up of two heavy chains and two light chains. The unique variable region allows ... Opsonization: Coating antigen with antibody enhances phagocytosis. *Antibody-dependent cell-mediated cytotoxicity: Antibodies ... Passive - Antibodies pass from mother to fetus via placenta or infant via the mother's milk.. Passive - Preformed antibodies in ... An antigen (short for antibody generator), is defined as any substance that binds to a specific antibody and elicits an ...
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 ...
"Breadth of neutralizing antibody response to human immunodeficiency virus type 1 is affected by factors early in infection but ... Blish that have been cited ~100 or more times are: "Genetic and environmental determinants of human NK cell diversity revealed ... October 2013). "Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry". Science ... July 2015). "Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility". Science ...
... the isolation of rare broad neutralizing HIV antibodies and their ancestor antibodies; and 8) the development of a new strategy ... the design of mosaic T cell and B cell Env vaccine candidates to overcome HIV diversity; 6) the discovery of the immune ... He led the group that deciphered the maturation pathways of several types of broadly neutralizing antibodies that point the way ... Bonsignori, Mattia (March 2, 2016). "Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody". Cell ...
... the PfRH5 antigen appears to have little genetic diversity. It was found to induce very low antibody response in people ... Antibodies that interfere with the binding, by either targeting the key region of the DARC or the DBP will prevent the ... Antibodies against the Schizont Egress Antigen-1 (PfSEA-1) were found to disable the parasite ability to rupture from the ... Antibodies are part of the specific immune response. They exert their effect by activating the complement cascade, stimulating ...
Lytle C, Xu JC, Biemesderfer D, Forbush B (December 1995). "Distribution and diversity of Na-K-Cl cotransport proteins: a study ... with monoclonal antibodies". Am. J. Physiol. 269 (6 Pt 1): C1496-505. doi:10.1152/ajpcell.1995.269.6.C1496. PMID 8572179. Gamba ...
Khan TA, Friedensohn S, de Vries AR, Straszewski J, Ruscheweyh HJ, Reddy ST (2016). "Accurate and predictive antibody ... J diversity. TCR gamma genes, in CD8+CD45RO+ memory T cells in blood: estimates range from 40,000 to 100,000 sub-types in ... "A direct estimate of the human alphabeta T cell receptor diversity". Science. 286 (5441): 958-61. doi:10.1126/science.286.5441. ...
Superseded theories in science
Germ line theory, explained immunoglobulin diversity by proposing that each antibody was encoded in a separate germline gene. ...
V(D)J recombination is the process by which the large variation in antibody binding sites is created. In this mechanism, DNA is ... Transposons may have an effect on the promotion of genetic diversity of many organisms. DNA transposons can drive the evolution ... "Gene duplication and exon shuffling by helitron-like transposons generate intraspecies diversity in maize". Nature Genetics. 37 ... recombined in order to create genetic diversity. Because of this, it has been hypothesized that these proteins, particularly ...
Antibody 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 ...
A 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: ...
Study shows how the immune system achieves antibody diversity
... especially when it comes to antibodies. Its long been known that a gene assembly process called V(D)J recombination allows our ... immune system to mix and match bits of genetic code, generating new antibodies to conquer newly encountered threats. ... Diversity is good, especially when it comes to antibodies. Its long been known that a gene assembly process called V(D)J ... Tags: Antibodies, Antibody, Cancer, Cell, Children, Chromatin, Cohesin, DNA, Gene, Genetic, Hospital, Immune System, Medicine, ...
The 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, ...
Genetic 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 ...
Newly identified B-cell selection process adds to understanding of antibody diversity | EurekAlert! Science News
Findings from Beth Israel Deaconess Medical Center add a new dimension to our understanding of antibody repertoires and their ... Newly identified B-cell selection process adds to understanding of antibody diversity. Beth Israel Deaconess Medical Center ... Newly identified B-cell selection process adds to understanding of antibody diversity Using high-throughput sequencing, ... 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 ...
Antibody Repertoire: Embracing Diversity | Science Translational Medicine
Antibody Repertoire: Embracing Diversity Message Subject. (Your Name) has forwarded a page to you from Science Translational ... Adjuvanted formulations expand the vaccine-induced antibody repertoires against a virus and a parasite. ... Adjuvanted formulations expand the vaccine-induced antibody repertoires against a virus and a parasite. ...
CiteSeerX - 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 ...
Study 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 ...
Antibody 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 ...
Surprising 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, ...
PPT - 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: ...
Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis isolates. | Journal of Clinical Microbiology
Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis isolates.. A Pantosti, R Colangeli, A O Tzianabos ... Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis isolates.. A Pantosti, R Colangeli, A O Tzianabos ... Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis isolates.. A Pantosti, R Colangeli, A O Tzianabos ... Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis isolates. Message Subject (Your Name) has ...
Transcription versus recombination in the generation of antibody diversity | IPBS
The huge diversity of antibodies is primarily generated through a process called V(D)J recombination, which involves DNA breaks ... Transcription versus recombination in the generation of antibody diversity. The huge diversity of antibodies is primarily ... B lymphocytes play a crucial role in adaptive immunity through their exclusive capacity to produce antibodies. The antibody ... diversity) and J (junction) segments. At the IgH locus, V(D)J recombination occurs in two steps, both catalyzed by the RAG ...
A Diversity of Antibody Epitopes Can Induce Signaling Through the Erythropoietin Receptor | Molecular Devices
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 ...
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 ...
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 ...
Distribution and Diversity of Na-K-Cl Cotransport Proteins: A Study With Monoclonal Antibodies - PubMed
We developed six monoclonal antibodies (designated T4, T8, T9, T10, T12, and T14) against a fusion protein fragment ... Distribution and Diversity of Na-K-Cl Cotransport Proteins: A Study With Monoclonal Antibodies C Lytle 1 , J C Xu, D ... Distribution and Diversity of Na-K-Cl Cotransport Proteins: A Study With Monoclonal Antibodies C Lytle et al. Am J Physiol. Dec ... These T antibodies selectively recognized putative NKCC proteins in a diverse variety of animal tissues. Western blot analysis ...
Single scaffold antibody libraries created with high rates of mutagenesis or diversity focused for peptide recognition
... ... These positions and others were varied to incorporate the natural diversity of other anti-peptide antibodies. The second ... This dissertation describes several strategies used to create diversity in non-immune antibody libraries. Two of the strategies ... Additionally, all of the contact residues of this antibody are commonly used contact residues in other anti-peptide antibodies ...
HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly...
Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody ... Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env ... Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide ...
Linkage of Natural Antibody Immunologic Homeostasis to Anticipatory Protection against a Common Pathogen Requires Natural...
Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice ... Specific H chain junctional diversity may be required for non-T15 antibodies to bind phosphorylcholine. J Immunol. 1988; 141: ... Changing the germline sequence of the DH locus thus permitted production of both anti-OxLDL antibodies and anti-PC antibodies, ... Tonegawa S. Somatic generation of antibody diversity. Nature. 1983;302: 575-581. ...
ANTIBODY DIVERSITY - HOW MANY ANTIBODY GENES - MRC Weatherall Institute of Molecular Medicine
Antibody - Wikipedia
This serves to increase the diversity of the antibody pool and impacts the antibodys antigen-binding affinity. Some point ... Antibody mimetic. Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens. They are ... Asymmetrical antibodies. Heterodimeric antibodies, which are also asymmetrical and antibodies, allow for greater ... How Lymphocytes Produce Antibody from Cells Alive!. *Antibody applications Fluorescent antibody image library, University of ...
Antibodies - Latest research and news | Nature
Fighting influenza through hemagglutinin diversity A multivalent vaccine that presents diverse influenza virus subtype H1 ... Antibodies. Definition. Antibodies are secreted immunoglobulin molecules produced mainly by plasma cells. The antigen-binding ... Migrant memory B cells secrete luminal antibody in the vagina In a mouse model of herpes simplex 2 virus infection, circulating ... Characterisation of a human antibody that potentially links cytomegalovirus infection with systemic lupus erythematosus *Jie ...
Paratope diversity of anti-prothrombin antibodies | Arthritis Research & Therapy | Full Text
Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. - Radcliffe Department of Medicine
May 1982 - Scientific American
Twist Bioscience, Distributed Bio Partner on Therapeutic Antibody Design Platform | GenomeWeb
Researchers say increased diversity in genomic studies will benefit all, PBS NewsHour reports. ... NEW YORK (GenomeWeb) - Twist Bioscience has signed a deal to offer its customers therapeutic antibody design and optimization ... Twist Bioscience, Distributed Bio Partner on Therapeutic Antibody Design Platform. Oct 11, 2016 ...
Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies | PNAS
2009) Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458(7238):636 ... Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies ... Antibodies are essential for the success of most vaccines (1), and antibodies against HIV appear to be the only correlate of ... S8). PGT128, and to a lesser extent 2G12, but not the CD4bs and CD4i antibodies, diminished the binding of all four antibodies ...
RepertoireImmunoglobulinGenesSpecificityRepertoiresProduction of antibodiesProteinsAntigensDifferent antibodiesMoleculesProduce antibodiesType of antibodyHeavy chainsGeneNeutralizing Antibody ConsortiumChainsSecreteHuman antibodyResponsesSingle antibodyProteinSerumSegmentsAffinity maturationCombinatorialBindsMonoclonal antibodySomatic hypermutationLymphocytesVariety of antibodiesIsotypesRecombinationSequencesImmunologyGenetics of antibody diversityEpitopeSpecific antibodiesCellsBindBroadly neutraliTherapeuticRegion of the antibodyClonalBnAbsCharacterizationLibrariesStrainsGermline antibodyInfectionAntigen -bindImmune response
- Even in the absence of antigen stimulation, a human can probably make more than 10 12 different antibody molecules-its preimmune antibody repertoire . (nih.gov)
- The immune system uses many strategies to generate its enormous repertoire of diverse antibodies, but their relative importance is not understood. (psu.edu)
- Here we address the contribution of antibody gene libraries to the antibody repertoire. (psu.edu)
- The B cells of the immune system produce a standard repertoire of millions of "germline" antibodies even in the absence of infection. (infectioncontroltoday.com)
- In adults and children, MF59 selectively enhanced antibody responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire. (sciencemag.org)
- In addition to the antibody epitope repertoire, we have investigated antibody affinity using 7 M urea resistance and calculated antibody off-rate constants by surface plasmon resonance (SPR). (sciencemag.org)
- A close inspection of the initial IgM repertoire reveals an asymmetric distribution of diversity, with CDR-H3 carrying the majority of the load. (jscimedcentral.com)
- The power of the V (D) J rearrangement mechanisms used to create diversity has led to a commonly held view that the naïve Ig repertoire consists of a collection of randomly generated antigen binding sites . (jscimedcentral.com)
- In this study, we analyzed the repertoire and specificity of antibodies to AM by using AM-binding murine monoclonal antibodies (MAbs) and human serum samples. (elsevier.com)
- Consequently, these processes not only develop the antibody repertoire but also solve some other problems of the adaptive immune response. (semanticscholar.org)
- In this perspective, we describe some of the strategies and considerations we use for manipulating the immune systems of transgenic animal platforms (such as XenoMouse ® ) with a focus on maximizing the diversity of the primary response and steering the ensuing antibody repertoire toward a desired outcome. (frontiersin.org)
- We will then draw from our experience using XenoMouse ® to discover novel human therapeutics and focus on the approaches we use to maximizing the diversity of the primary antibody repertoire and to steer it toward the desired outcome. (frontiersin.org)
- The collection of unique B cells in an organism (the B-cell repertoire) encodes and produces the corresponding antibody repertoire. (frontiersin.org)
- Herein, we will use "antibody repertoire" to describe the collection of sequence-unique antibodies, and their corresponding B cells, present in a given system. (frontiersin.org)
- Repertoire sequencing studies of bovine antibody heavy chain variable sequences revealed that bovine antibodies can contain heavy chain complementarity determining region 3 (CDRH3) loops with 60 or more amino acids, with complex structures stabilized by multiple disulfide bonds. (elsevier.com)
- Rearrangement and assembly of B cell antigen receptor genes generates a diverse antibody repertoire in humans and mice. (rupress.org)
- In the 1980s, the structure of the mouse Ig loci and the mechanisms by which the antibody repertoire is diversified were defined ( 6 ). (rupress.org)
- This explanation for the generation of a diverse naive antibody repertoire was so seemingly complete that there appeared to be no room or requirement for alternative or additional mechanisms. (rupress.org)
- High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. (sciencemag.org)
- Variability in the developing antibody repertoire is focused on the third complementarity determining region of the H chain (CDR-H3), which lies at the center of the antigen binding site where it often plays a decisive role in antigen binding. (uab.edu)
- This concept of a repertoire of random antigen binding sites is inconsistent with the observation that diversity (DH) gene segment sequence content by reading frame (RF) is evolutionarily conserved, creating biases in the prevalence and distribution of individual amino acids in CDR-H3. (uab.edu)
- IgG-switched memory B cells in IL-6 knock-in mice displayed a diverse antibody repertoire and high specificity against immunized antigen. (bloodjournal.org)
- Based on their findings, they estimated that the human antibody repertoire is much greater than previously thought-with the potential for the body to make a quintillion, or one million trillion, unique antibodies. (nih.gov)
- Antibody repertoire information could soon be used to diagnose autoimmune diseases and chronic infections, for example, or to design vaccines," Briney says. (nih.gov)
- Additional studies are needed to more accurately determine the full scope of the human antibody repertoire. (nih.gov)
- Commonality despite exceptional diversity in the baseline human antibody repertoire. (nih.gov)
- This process results in an immunoglobulin gene that encodes an antibody of a different isotype. (news-medical.net)
- Retrieved on May 22, 2019 from https://www.news-medical.net/health/Antibody-Immunoglobulin-Diversity.aspx. (news-medical.net)
- Development and function of the immunoglobulin-producing system: I. Effect of bursectomy at different stages of development on germinal centers, plasma cells, immunoglobulins and antibody production. (springer.com)
- Dr. Leder later found out that an antibody-producing B cell methodically rearranges the two genes which encode the light chain portion of the immunoglobulin molecule. (laskerfoundation.org)
- Then he created a radiolabeled probe from antibody messenger RNA to search for the immunoglobulin-producing genes in the two masses of DNA fragments. (laskerfoundation.org)
- An antibody ( Ab ), also known as an immunoglobulin ( Ig ),  is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses . (wikipedia.org)
- Antibodies are glycoproteins belonging to the immunoglobulin superfamily . (wikipedia.org)
- Antibodies are secreted immunoglobulin molecules produced mainly by plasma cells. (nature.com)
- Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. (ox.ac.uk)
- Combinatorial association of immunoglobulin gene elements is the most important process in the creation of extreme diversity of antibody molecules. (semanticscholar.org)
- 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. (semanticscholar.org)
- Select the true statements regarding antibody (specifically, immunoglobulin G) structure.1. (clutchprep.com)
- The basic functional unit of an antibody is an immunoglobulin monomer, but antibodies secreted from plasma cells are typically dimeric with occasional higher order structures. (proteopedia.org)
- There are two types of immunoglobulin light chains in mammals, labeled lambda and kappa, with only one represented in each antibody. (proteopedia.org)
- the terms antibody and immunoglobulin are often used interchangeably. (wikipedia.org)
- Antibody diversity is first generated by rearrangement of immunoglobulin (Ig) genes during B cell development in the bone marrow, and later by antigen-driven diversification in germinal centers (GCs). (rupress.org)
- In that trial, antibodies of the type called immunoglobulin G (IgG) seemed protective, working by stimulating antibodies that did not themselves neutralise HIV but induced the immune system to mount a generalised attack on it. (aidsmap.com)
- A second type of antibody, of the immunoglobulin A (IgA) type, was positively unhelpful, correlating with increased infection. (aidsmap.com)
- Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal carcinoma (NPC) and control subjects, by use of immunofluorescence assay (IFA). (vumc.nl)
- In particular, the PreB stage represents the phase during which immunoglobulin (Ig) genes, which code for the antibody molecules, rearrange their DNA segments in order to produce functional genes. (frontiersin.org)
- One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. (ajtmh.org)
- The genes coding for these diverse range of immunoglobulins however are limited and do not number similar to the variety of antibodies. (news-medical.net)
- To create the variety of antibodies thus the body adopts complex mechanisms from the relatively small number of antibody genes. (news-medical.net)
- Each of the genes for the antibodies are located on specific location (loci) on the chromosomes. (news-medical.net)
- There are several distinct genes for each domain of the antibody. (news-medical.net)
- When combined, these genes can yield a large variety of combinations for antibodies by permutation and combination. (news-medical.net)
- The genes coding for the antibodies in these B cells undergo high rate of point mutation or point changes in genetic codes for antibodies. (news-medical.net)
- Somatic translocation of antibody genes. (springer.com)
- Antibodies are proteins, and proteins are encoded by genes. (nih.gov)
- Antibody diversity therefore poses a special genetic problem: how can an animal make more antibodies than there are genes in its genome ? (nih.gov)
- He has been instrumental in documenting in elegant detail the immune system's method of rearranging pre-existing sequences of DNA to make the genes for each new antibody. (laskerfoundation.org)
- In addition, Dr. Hood found that random genetic changes, introduced as the genes are built, add still another dimension to the rich variability of antibody genes. (laskerfoundation.org)
- Dr. Tonegawa conceived and performed a creative series of experiments to determine whether an individual inherits a single, predetermined gene for each type of antibody made during his lifetime, or whether the immune system rearranges genetic information to create new genes responsible for the production of each type of antibody. (laskerfoundation.org)
- Thus, in one crucial experiment, Dr. Tonegawa determined the genetic mechanism of antibody diversity and showed that new genes are created through rearrangement of DNA during B-cell differentiation. (laskerfoundation.org)
- In further research, Dr. Tonegawa confirmed and determined the details of his discovery by cloning and sequencing antibody genes. (laskerfoundation.org)
- To Dr. Tonegawa, for proving brilliantly that antibody diversity is the result of an ordered system of gene rearrangement, and for demonstrating that the DNA responsible for antibody production is routinely reorganized to create new genes during the lifetime of an individual, this 1987 Albert Lasker Basic Medical Research Award is given. (laskerfoundation.org)
- 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 subsets called V, D and J. The most diverse part of an antibody is the region where the three genes come together, a stretch called the third complementarity-determining region, or CDR3. (eurekalert.org)
- They found that B cells for which antibodies use V genes that encode 'looser' elbows were more likely to mature, regardless of their CDR3 sequence. (eurekalert.org)
- H chain diversity: 38 to 46 IGHV genes, 23 to 27 IGHD genes and 6 IGHJ genes able to produce 5244 to 7452 possible H-chain variable-region combinations. (avroarrow.org)
- L-chain diversity: 30 to 44 IGKV genes, 5 IGKJ genes or 150 to 220 possible ϰ L-chain variable regions, 29 to 33 IGLV genes and 4 to 5 IGLJ genes, or 116 to l65 possible λ L-chain variable regions. (avroarrow.org)
- But when one of those B cells encounters a matching target (such as a specific shape on a virus) and responds by becoming activated and replicating rapidly, its antibody-coding genes mutate slightly with each cell division. (infectioncontroltoday.com)
- The antibody heavy and light chain loci undergo a complex and ordered series of DNA breaks/fusions called V(D)J recombination that enables a combinatorial assembly of different gene segments, ultimately leading to the genes that encode the antibody chains (see figure). (ipbs.fr)
- Although a huge variety of different antibodies is made in a single individual, the number of genes available to make these proteins is limited by the size of the genome . (wikipedia.org)
- These allow vertebrate B cells to generate a huge pool of antibodies from a relatively small number of antibody genes. (wikipedia.org)
- The variety of antibodies is got by combining segments from a pool of genes in many different ways. (wikipedia.org)
-   Antibody genes also re-organize in a process called class switching , which allows a single antibody to be used by several different parts of the immune system. (wikipedia.org)
-   Antibody genes also re-organize in a process called class switching that changes the base of the heavy chain to another, creating a different isotype of the antibody that retains the antigen specific variable region. (wikidoc.org)
- By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. (sciencemag.org)
- The team grouped the antibodies into "clonotypes" based on the similarities of the genes that make up the heavy chain. (nih.gov)
- Several useful theories on the development of antibody heterogeneity taking into account the diversity and specificity of antibody molecules, the restrictions imposed by genetic and structural analyses, and the phenomenon of self-recognition have been proposed. (springer.com)
- This ability allows the B cell to switch from making membrane -bound antibody to making secreted antibody, or from making one class of antibody to making another, all without changing the antigen-specificity of the antibody. (nih.gov)
- The individual nucleotides in VJ or VDJ units are replaced with alternative bases thus most likely altering the specificity of the encoded Ig (Generation of Ab Diversity, n.d. (avroarrow.org)
- Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity, diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. (sciencemag.org)
- Murine MAbs were found to be diverse in their specificity to AM and cross-reactivity with other arabinose-containing mycobacterial polysaccharides, with MAb 9d8 binding exclusively to AM. Human antibodies to AM were detected in serum samples from patients with pulmonary tuberculosis (TB), as well as in those from healthy, purified protein derivative-negative controls, with significantly higher titers among patients. (elsevier.com)
- Antibody generation in vivo offers several advantages, including the ability to readily recover molecules that bind to the target antigen with high specificity and affinity ( 1 ). (frontiersin.org)
- Each plasma cell is programmed to make an antibody of a single specificity, which it releases into the blood. (proteopedia.org)
- The amazing specificity antibodies operate with is made possible by the physical structure of the antibody, which appears simplistic, but contains several levels of additional complexity. (proteopedia.org)
- Antibodies are highly sought after for diagnostic applications owing to its specificity and affinity towards a target antigen. (intechopen.com)
- Intestinal anti-TG2 antibody production does not show absolute specificity for CD. (mdpi.com)
- 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 repertoires - each individual's complement of millions of B cells -- and the potential for shaping these repertoires to better fight disease. (eurekalert.org)
- We initially wanted to ask how selection on CDR3 changed antibody repertoires during B-cell maturation," says Arnaout. (eurekalert.org)
- Ultimately, the authors write, "This discovery adds a surprising new dimension to the understanding of antibody repertoires and might one day help us shape them ourselves. (eurekalert.org)
- Adjuvanted formulations expand the vaccine-induced antibody repertoires against a virus and a parasite. (sciencemag.org)
- We use the genetic algorithm as a model of evolution to investigate the type of antibody repertoires that might evolve in relation to a given pathogenic environment. (psu.edu)
- The expanded antibody repertoires correlated with an increase in the titer of antibodies reactive with native HA and with viral neutralization (VN) ( 13 ). (sciencemag.org)
- We have recently tested the relative roles of germline versus somatic selection of CDR-H3 sequence in the generation and function of the natural antibody (NAb) repertoires. (jscimedcentral.com)
- The antibody mining toolbox: an open source tool for the rapid analysis of antibody repertoires. (semanticscholar.org)
- The creation of transgenic animal platforms expressing human antibody repertoires has revolutionized therapeutic antibody drug discovery. (frontiersin.org)
- These challenges have been met with a number of novel approaches focused on the generation of large, high-quality, and diverse antibody repertoires. (frontiersin.org)
- We will first concentrate on the transgenic platforms and call out specific features that contribute to forming antibody repertoires. (frontiersin.org)
- Antigen recognition by mammalian antibodies represents the most diverse setting for protein-protein interactions, because antibody variable regions contain exceptionally diverse variable gene repertoires of DNA sequences containing combinatorial, non-templated junctional mutational diversity. (elsevier.com)
- Humoral immune response profiling has progressed greatly in recent years owing to advancements in next-generation sequencing (NGS) technology and bioinformatic analysis of antibody repertoires ( 1 - 4 ). (sciencemag.org)
- High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. (royalsocietypublishing.org)
Production of antibodies4
-  The production of antibodies is the main function of the humoral immune system . (wikipedia.org)
- To gain a more thorough understanding of the humoral aspect of this autoimmunity, we investigated the cellular and molecular basis of the production of antibodies to various citrullinated autoantigens in RA patients. (rupress.org)
- The cross-talk results in collaboration between B and T cells and production of antibodies directed against the antigen. (pnas.org)
- The in vivo production of antibodies by B-cells involves a series of intricate gene editing processes resulting in a highly diverse pool of antibodies. (intechopen.com)
- 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)
- These T antibodies selectively recognized putative NKCC proteins in a diverse variety of animal tissues. (nih.gov)
- Proteins identified previously as Na-K-Cl cotransporters by loop diuretic photoaffinity labeling were mutually recognized by multiple T antibodies. (nih.gov)
- Antibodies , also known as Immunoglobulins (Ig) are gamma globulin proteins, primarily found in the blood of vertebrates. (proteopedia.org)
- Antibodies (also called immunoglobulins ) are large Y-shaped proteins . (wikipedia.org)
- Antibodies are proteins the body makes to target and help eliminate viruses, but it can take weeks for the best ones to form after an infection occurs. (wect.com)
- Antibodies (also known as immunoglobulins  ) are proteins that are found in blood or other bodily fluids of vertebrates , and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses . (wikidoc.org)
- Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. (rupress.org)
- We then measured antibodies to three allelic AMA1 proteins (AMA1_3D7, AMA1_FVO, and AMA1_HB3) and used competition enzyme-linked immunosorbent assays (ELISAs) to analyze allele-specific antibodies. (ox.ac.uk)
- Antibody proteins can physically change their shape to bind different epitopes, 5. (mympsc.com)
- In English Technologies to develop and evolve the function of proteins and, in particular, antibodies have developed rapidly since the introduction of phage display. (lu.se)
- 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)
- Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. (hindawi.com)
- Phage display 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 Richard Lerner and Carlos Barbas and the German Cancer Research Center with Frank Breitling and Stefan Dübel for display of proteins such as antibodies for therapeutic protein engineering. (wikipedia.org)
- Due to diversity in microbes, the antibody needs to adopt variations to allow their interactions with many different antigens. (news-medical.net)
- Antibodies are protein molecules essential to the body's defense against potentially harmful organisms and substances, which are known as antigens. (laskerfoundation.org)
-  This enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an equally wide variety of antigens. (wikipedia.org)
- which seperates the lobes of the antibody from one another and provides ample flexibility to bind antigens effectively. (proteopedia.org)
-  This enormous diversity of antibodies allows the immune system to recognize an equally wide variety of antigens. (wikipedia.org)
- Here, we demonstrate a high-dynamic-range quantification of antibody binding to single antigens in a multiplexed suspension bead array format. (bioportfolio.com)
- Peptide microarrays that display overlapping peptide scans through antigens from infectious organisms or tumor associated antigens for antibody or serum profiling. (jpt.com)
- The presence of specific antibodies in vaccinated mice serum was studied by immunoblot analysis at different days after vaccination and showed an intensive immune response to a wide range of antigens with molecular weight ranging between 22 and 250 kDa. (hindawi.com)
- Monoclonal antibody therapy has also shown high efficacy against tumour-specific antigens in some cancers [ 8 - 12 ]. (royalsocietypublishing.org)
- Antibodies attach themselves to the antigens on the surface of cancerous cells. (wikipedia.org)
- Human, for example, generate about 10 billion different antibodies. (news-medical.net)
- This is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. (news-medical.net)
- This means generation of distinctly different antibodies due to different variable domains on the antibodies. (news-medical.net)
- Dr. Hood investigated the variable part of the light chains of different antibodies and found their chemical structures belonged to three distinct families. (laskerfoundation.org)
- The big question:how do you get all those different antibodies? (slideserve.com)
- There are a vast number of microbe strains, and so vertebrates need millions of different antibodies. (wikipedia.org)
-  Actually, humans generate about 10 billion different antibodies, each capable of binding a distinct antigen site. (wikipedia.org)
- It protects its vulnerable sites with a surface envelope protein (Env) that can mutate rapidly from strain to strain and coats its surface with covalently linked sugar molecules (glycans) that are hard for antibodies to grip. (infectioncontroltoday.com)
- Therapeutic molecules derived from antibodies have become a dominant class of drugs used to treat human disease. (frontiersin.org)
- These epitopes bind with their antibody in a highly specific interaction, called induced fit , that allows antibodies to identify and bind only their unique antigen in the midst of the millions of different molecules that make up an organism . (wikidoc.org)
- B cells use membrane-bound antibody as part of their antigen receptor while T cells use a different receptor that recognizes antigen fragments bound to MHC molecules. (pnas.org)
- ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. (wikipedia.org)
- We begin this section by discussing the mechanisms that B cells use to produce antibodies with an enormous diversity of antigen -binding sites. (nih.gov)
- B cells produce antibodies that circulate in the bloodstream. (avroarrow.org)
- B lymphocytes play a crucial role in adaptive immunity through their exclusive capacity to produce antibodies. (ipbs.fr)
- The processes of in vivo sequence diversification, antigen-driven somatic hypermutation, and numerous quality control checkpoints ensure the non-random selection and enrichment of B cells that produce antibodies with therapeutically desirable properties ( 2 - 5 ). (frontiersin.org)
Type of antibody1
- We now know that each type of antibody chain-κ light chains, λ light chains, and heavy chains-has a separate pool of gene segments and exons from which a single polypeptide chain is eventually synthesized. (nih.gov)
- Recall that the variable regions of both the light and heavy chains of antibodies usually form the antigen - binding site . (nih.gov)
- Thus dissimilar combinations of light and heavy chains within individual B cells add further diversity. (avroarrow.org)
- There are several different types of antibody heavy chains that define the five different types of crystallisable fragments (Fc) that may be attached to the antigen-binding fragments. (wikipedia.org)
- We have prepared large libraries with such properties by using random oligonucleotide synthesis, which has the potential to create approximately 10(20) complementarity-determining regions for antibody heavy chains. (scripps.edu)
- Crowe, James E. / Structural diversity of ultralong CDRH3s in seven bovine antibody heavy chains . (elsevier.com)
-  Antibodies are typically made of basic structural units-each with two large heavy chains and two small light chains . (wikipedia.org)
- There are several different types of antibody heavy chains, and several different kinds of antibodies, which are grouped into different isotypes based on which heavy chain they possess. (wikipedia.org)
- each antibody has two large heavy chains H and two small light chains L . Antibodies are produced by a kind of white blood cell called a B cell . (wikidoc.org)
- Antibody consists of two heavy chains and two light chains. (creative-biolabs.com)
- Illustration of antibodies, with heavy chains in blue and light chains in white. (nih.gov)
- It's long been known that a gene assembly process called V(D)J recombination allows our immune system to mix and match bits of genetic code, generating new antibodies to conquer newly encountered threats. (news-medical.net)
- The RAG 1/2 complex first binds to a site on an antibody gene known as the 'recombination center. (news-medical.net)
- The loop extrusion process is harnessed by antibody gene loci to properly present substrate gene segments to the RAG complex for V(D)J recombination. (news-medical.net)
- While these findings have been made in the context of V(D)J recombination in antibody formation, they have implications for processes that could be involved in gene regulation more generally,' says Alt. (news-medical.net)
- Each pool is on a different chromosome and contains a large number of gene segments encoding the V region of an antibody chain and, as we saw in Figure 24-33 , a smaller number of exons encoding the C region. (nih.gov)
- In addition to bringing together the separate gene segments and the C-region exons of the antibody gene, these rearrangements also activate transcription from the gene promoter through changes in the relative positions of the enhancers and silencers acting on the promoter. (nih.gov)
- To Dr. Leder, for his studies of the genetics of antibody diversity, which led to his profound discovery that cancer can result from a disruption in gene regulation, this 1987 Albert Lasker Basic Medical Research Award is given. (laskerfoundation.org)
- Combinatorial joining of gene segments magnifies antibody diversity by random rearrangement of VJ and VDJ in somatic cells. (avroarrow.org)
- The huge diversity of antibodies is primarily generated through a process called V(D)J recombination, which involves DNA breaks/fusions of distant gene segments on the chromosome. (ipbs.fr)
- V(D)J recombination targets the variable region which contains multiple clusters of gene segments : V (variable), D (diversity) and J (junction) segments. (ipbs.fr)
- 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)
- 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)
- 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)
- First in inverse order of importance, the rearrangement of the variable (V), diversity (D) and joining (J) gene segments permits VDJ rearrangement to create a ten to twenty-fold increase in combinatorial V domain diversity in the heavy chain. (jscimedcentral.com)
-  The large and diverse population of antibody paratope is generated by random recombination events of a set of gene segments that encode different antigen-binding sites (or paratopes ), followed by random mutations in this area of the antibody gene, which create further diversity. (wikipedia.org)
- Then, hyper - mutations occur in the binding site area of the antibody gene. (wikipedia.org)
-  The large and diverse population of antibodies is generated by random combinations of a set of gene segments that encode different antigen binding sites (or paratopes ), followed by random mutations in this area of the antibody gene, which create further diversity. (wikipedia.org)
- Diversity generated through combinatorial joining of Ig gene segments, with the addition of untemplated nucleotides at the joining ends, was calculated to provide binding sites sufficient to accommodate an almost infinite number of possible antigenic determinants ( 6 ). (rupress.org)
- Moreover, among samples that were positive for the DEC types enteroaggregative E. coli, enteropathogenic E. coli and enterotoxigenic E. coli (ETEC) carrying the eltB gene, the diversities were almost as high as among non-DEC samples, whereas samples positive for ETEC carrying estA, enteroinvasive E. coli and enterohaemorrhagic E. coli showed lower diversities, indicating the prevalence of virulent clonal groups among these samples. (nih.gov)
- Anti-TG2 antibodies are produced primarily at an intestinal level by specific B lymphocytes and, using phage display library technology, it has been proven that these antibodies are synthesized in CD patients with preferential use of IGVH5-51 gene family [ 3 ]. (mdpi.com)
Neutralizing Antibody Consortium2
- 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)
- Scientists at NIAID and the IAVI Neutralizing Antibody Consortium of The Scripps Research Institute in La Jolla, California, previously isolated these individual antibodies from people living with HIV. (scienceblog.com)
- During the development of a B cell, a complete coding sequence for each of the two antibody chains to be synthesized is assembled by site-specific genetic recombination (discussed in Chapter 5). (nih.gov)
- When combined with light chains and expressed on phage surfaces, high-affinity antibodies could be selected from 5.0 x 10(7) Escherichia coli transformants. (scripps.edu)
- Most of the available information on the antibody problem emerged from analyses of relatively mature cells of the plasma cell lineage and the end products they secrete. (springer.com)
- The increased abundance of IL-10 in HF-preconditioned mice correlated with enhanced GC responses and may promote the establishment of long-lived plasma cells that secrete antigen-specific, high-affinity antibodies. (sciencemag.org)
-  Activated B cells differentiate into either antibody generating factories called plasma cells that secrete soluble antibody, or into memory cells that survive in the body for years afterwards to allow the immune system to remember an antigen and respond faster upon future exposures. (wikidoc.org)
- The B lymphocyte's antigen receptor is a membrane-bound version of the antibody it will secrete if activated. (encyclopedia.com)
- B cells evolve on the time scale of pathogen populations and secrete pathogen-specific antibodies that protect us from infection. (royalsocietypublishing.org)
- The remarkable capacity of engineered animals to utilize human antibody sequences to functionally replace their own has allowed researchers to harness the power of the natural humoral immune response. (frontiersin.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)
- 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)
- 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)
- Known to activate the nutrient-sensing kinase GCN2, HF promoted phosphorylation of the translation initiation factor eIF2α in immune cells, increased germinal center formation, and increased neutralizing antibody responses. (sciencemag.org)
- Here, we showed that mimicking AAR with halofuginone (HF) enhanced the magnitude and affinity of neutralizing, antigen-specific antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a potent vaccine candidate against DENV. (sciencemag.org)
- and they trigger destruction of pathogens by stimulating the complement pathway or by Antibody Dependent Cell-mediated Cytotoxicity , among other immune responses. (proteopedia.org)
- There are three branches of the immune system, the antibody response, the cellular response and the innate response, and in each case these responses may vary by type, by strength, and by how broad they are (a vaccine would need to work against most different strains of HIV). (aidsmap.com)
-  Antibodies are, therefore, an essential component of the adaptive immune system that learns, adapts and remembers responses to invading pathogens. (wikidoc.org)
- Allelic diversity and naturally acquired allele-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 in Kenya. (ox.ac.uk)
- however, our understanding of how antibody specificities relate to B cell function remains limited due to the complexity of polyclonal antibody responses. (bioportfolio.com)
- We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis -infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). (ajtmh.org)
- However, the existing models cannot support robust adaptive immune responses, especially the generation of class-switched, antigen-specific antibody responses. (bloodjournal.org)
- 2 ⇓ - 4 However, the generation of class-switched, antigen-specific antibody responses by human B cells is still a major challenge. (bloodjournal.org)
- Although antigen-specific human IgM antibody responses are generated, the achievement of affinity maturation and class-switching from the IgM to the IgG isotype has been particularly difficult. (bloodjournal.org)
- The concept of having a single antibody that binds to three unique sites on HIV is certainly an intriguing approach for investigators to pursue. (scienceblog.com)
- Earlier this month, the FDA gave emergency authorization to a single-antibody drug from Eli Lilly that also is still being studied. (wect.com)
- This allows a single antibody to be used by several different parts of the immune system. (wikidoc.org)
- We herein review some of the most prominent approaches in the field and in particular discuss specific features related to the development of antibody libraries based on single antibody framework scaffolds. (lu.se)
- 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. (eurekalert.org)
- We developed six monoclonal antibodies (designated T4, T8, T9, T10, T12, and T14) against a fusion protein fragment encompassing the carboxy-terminal 310 amino acids of the human colonic NKCC. (nih.gov)
- Most of the T antibodies effectively immunoprecipitated the denatured form of the NKCC protein. (nih.gov)
- Positions were chosen for variation based on their usage as contact residues in both anti-peptide and anti-protein antibodies. (utexas.edu)
- Though the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen-binding sites, to exist. (wikipedia.org)
- In our experiments, prothrombin was recognized by relevant antibodies when the protein was bound to phosphatidylserine-coated microtiter plates using calcium ions or when it was bound to high binding plates with or without calcium ions. (biomedcentral.com)
- Though the general structure of all antibodies is very similar, that small region at the tip of the protein is extremely variable. (wikipedia.org)
- Cows injected with a protein that mimics HIV's envelope make broadly neutralizing antibodies that inhibit multiple strains of the virus. (the-scientist.com)
- An antibody is a Y-shaped protein that's produced by white blood cells. (nih.gov)
- B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. (royalsocietypublishing.org)
- An anticancer drug is coupled to an antibody that specifically targets a certain tumor antigen (e.g. a protein that, ideally, is only to be found in or on tumor cells). (wikipedia.org)
- The biochemical reaction between the antibody and the target protein (antigen) triggers a signal in the tumor cell, which then absorbs or internalizes the antibody together with the linked cytotoxin. (wikipedia.org)
- However, MMAE linked to an anti-CD30 monoclonal antibody (cAC10, a cell membrane protein of the tumor necrosis factor or TNF receptor) was stable in extracellular fluid. (wikipedia.org)
- For both pandemic influenza vaccines, there was a close correlation between serum antibody affinity and virus-neutralizing capacity. (sciencemag.org)
- In summary, our study suggests that antibodies to AM are diverse and heterogeneous with respect to antigen recognition and V H , determinant expression, with human serum samples containing different subsets of antibodies to AM with the specificities of AM-binding murine MAbs. (elsevier.com)
- Unlike classical methods for antibody analysis (for example, serum titers), Ig-Seq offers the potential to capture quantitative molecular measurements of immunological phenomena related to clonal selection and expansion, such as clonal frequency, diversity, and somatic hypermutation. (sciencemag.org)
- We have investigated intestinal production of anti-TG2 antibodies in 136 patients with normal serum levels of anti-TG2 antibodies and normal duodenal mucosa. (mdpi.com)
- The presence in the serum of anti-tissue-transglutaminase 2 (anti-TG2) antibodies is considered a sensitive and specific biomarker for CD [ 2 ]. (mdpi.com)
- These are called variable (V), diversity (D) and joining (J) segments. (news-medical.net)
- CDR-H3 is created by the combinatorial rearrangement of variable (V H ), diversity (D H ), and joining (J H ) segments in conjunction with the variable insertion of random N nucleotides and the variable loss or P nucleotide gain of terminal nucleotide sequence ( 10 ). (jimmunol.org)
- The second library, the Hu:anti-pep, is based on a widely used, unique combination of human germline antibody segments that express well in bacterial expression. (utexas.edu)
- Such families are the products of a powerful diversity-extending process in the immune response called affinity maturation. (infectioncontroltoday.com)
- Moreover, MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. (sciencemag.org)
- The final strategy used to introduce diversity is widely used for affinity maturation of low affinity, previously selected antibodies. (utexas.edu)
- Combinatorial events in generation of antibody diversity. (semanticscholar.org)
- The properties of naiveté and large diversity are considered to be essential starting features for combinatorial antibody libraries that eschew immunization by evolution in vitro. (scripps.edu)
- Semisynthetic and ultimately totally synthetic combinatorial libraries when coupled with mutation and selection procedures should replace immunization for generation of reagent, therapeutic, and catalytic antibodies. (scripps.edu)
- When the antigen binds to the antibody and activates the B cells, they rapidly proliferate and each of these cells contains DNA for antibody formation. (news-medical.net)
- Each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor (except for IgD, which is essentially the BCR), thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds. (wikipedia.org)
- This new broadly neutralizing antibody binds to three different critical sites on HIV. (scienceblog.com)
- When a foreign antigen binds to a B-lymphocyte ( B-cell ), it activates the B-cell, and upon stimulation by helper T-cells , undergoes clonal proliferation and B-cell maturation into antibody forming plasma cells . (proteopedia.org)
- Numerous antibodies can be prepared, against one antigen, each binds to unique epitopes. (mympsc.com)
- Ig-seq has been used to address basic questions in B cell development and differentiation ( 5 - 9 ), and also as an application-focused tool for vaccine development ( 10 - 13 ), immunodiagnostic discovery ( 10 , 14 - 16 ), and monoclonal antibody engineering ( 17 - 23 ). (sciencemag.org)
- To address this, we developed the Spec-seq framework, which allows for simultaneous monoclonal antibody (mAb) characterization and transcriptional profiling from the same single cell. (bioportfolio.com)
- More recently, transfer of specific antibodies to patients infected with respiratory syncytial virus has demonstrated the feasibility of monoclonal antibody therapy during infection [ 6 , 7 ]. (royalsocietypublishing.org)
- Due to somatic hypermutation, the affinity of synthesized antibody increases even more. (semanticscholar.org)
- We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. (sciencemag.org)
- After several rounds of proliferation, somatic hypermutation begins, a process by which the Ig DNA becomes mutated under the action of activation-induced cytidine deaminase (AID), leading to the generation of diverse clones expressing antibodies with different, potentially higher, affinity for antigen. (frontiersin.org)
- However, the complete range of mechanisms that generate antibody diversity and produce lymphocytes with specific functional and tissue-specific properties remains controversial. (rupress.org)
Variety of antibodies2
- The five different types of Fc regions allow antibodies to be grouped into five isotypes . (wikipedia.org)
- Five different antibody isotypes are known in mammals. (wikipedia.org)
- Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter. (wikidoc.org)
- Antibodies can come in different varieties known as isotypes or classes. (wikidoc.org)
- This showed that the DNA sequences encoding an antibody molecule are rearranged at some stage in B cell development ( Figure 24-36 ). (nih.gov)
- Remarkably, antibodies selected only for binding displayed both general structural features known to be important in nature's own antibodies and specific consensus sequences thought to be critical for interaction with the hapten against which the library was selected. (scripps.edu)
- A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA + antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences. (rupress.org)
- Using large-scale genetic sequencing technologies and analytical software they developed, the researchers examined nearly 3 billion antibody heavy-chain sequences. (nih.gov)
- The emphasis in this discussion will be on early events in differentiation of antibody-producing cells, an area of immunology that is in its experimental infancy. (springer.com)
- The first immunology antibody-drug conjugate (iADC), ABBV-3373, is undergoing clinical trials for participants with moderate to severe rheumatoid arthritis. (wikipedia.org)
Genetics of antibody diversity1
- To Dr. Hood, whose prolific and detailed investigations have translated the genetics of antibody diversity into explicit molecular terms, this 1987 Albert Lasker Basic Medical Research Award is given. (laskerfoundation.org)
- The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. (osti.gov)
- Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. (physiciansweekly.com)
-   Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. (wikipedia.org)
- Ideal antibody candidates are often required to bind with high affinity to a specific epitope, cross-react to a non-human ortholog, lack binding to paralogs, and survive the rigors of the stringent drug development process ( 6 ). (frontiersin.org)
- The unique part of the antigen recognized by an antibody is called an epitope . (wikidoc.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)
- Study of influenza virus transmission in humans provides evidence that hemagglutinin stalk-specific antibodies correlate with protection from infection. (nature.com)
- These OVA-specific antibodies displayed the highest frequency of somatic mutation, further suggesting that human IL-6 is important for efficient B-cell activation and selection. (bloodjournal.org)
- Once the B cells are activated they produce different classes of antibody (IgA, IgE, or IgG). (news-medical.net)
- Those B cells that produce these strong antibodies as a result of the mutations are preserved and proliferated while the others die off. (news-medical.net)
- However, the paucity of knowledge of the origin, identity, and characterization of pre-antibody forming cells has been a handicap in the struggle toward a final solution of this problem. (springer.com)
- The new research, led by Frederick Alt, PhD, director of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children's Hospital, shows in exquisite detail how our immune system's B cells exploit the loop formation process for the purpose of making new kinds of antibodies. (news-medical.net)
- He used enzymes to break up the DNA from cells of the germ line and from antibody-making B cells of the same individual. (laskerfoundation.org)
- It starts producing antibodies that can grab or at least block the virus's most vulnerable sites-sites that don't change much from strain to strain because they are involved in crucial functions such as docking or fusing with host cells. (infectioncontroltoday.com)
- A family of not-quite-identical B cells and corresponding antibodies are generated that can potentially hit the same target more strongly and precisely-and also in different ways, hopefully blocking the ability of a virus to escape with mutations of its own. (infectioncontroltoday.com)
- Antibodies are secreted by B cells of the adaptive immune system, mostly by differentiated B cells called plasma cells . (wikipedia.org)
- The BCR is found only on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells that will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure. (wikipedia.org)
- In a mouse model of herpes simplex 2 virus infection, circulating memory B cells-rather than plasma cells-are shown to be the source of antibody secretion in the vaginal lumen following secondary infection. (nature.com)
- The three-pronged antibody, created by investigators from the National Institutes of Health (NIH) and the Paris-based pharmaceutical company Sanofi, also stopped a greater number of HIV strains from infecting cells in the laboratory more potently than natural, single antibodies. (scienceblog.com)
- The variable region of the heavy chain in antibodies is different for all antibodies created by different B-cells. (proteopedia.org)
- The Antibodies are secreted by plasma cells transformed from B cells, and each B cell line can produce only one specific antigenic determinant. (creative-biolabs.com)
- We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA + RA patients, whereas such antibodies were not found in ACPA − patients. (rupress.org)
- Under this view, the immune response is solely controlled by somatic positive and negative clonal selection mechanisms that act on individual B cells to promote production of protective antibodies and prevent the production of self-reactive antibodies. (uab.edu)
- Spec-seq unveils transcriptional subpopulations of antibody-secreting cells following influenza vaccination. (bioportfolio.com)
- They are the precursors for the antibody-secreting plasma cells and they also take up antigen, particularly antigen for which they bear-specifi. (bioportfolio.com)
- Plasma cells: the programming of an antibody-secreting machine. (bioportfolio.com)
- B cells can generate several types of antibody-secreting cells, including plasmablasts that divide and are short lived, as well as plasma cells that do not proliferate and can persist for extended tim. (bioportfolio.com)
- During the GC reaction, B cells undergo critical differentiation steps, which ultimately lead to the generation of antibodies with altered effector function and higher affinity for the selected antigen. (frontiersin.org)
- From there, the B cells (centroblasts) move to the adjacent region called the light zone (LZ), where they express their antibody on the cell surface. (frontiersin.org)
- B cells make the antibodies that neutralize or kill specific invaders. (nih.gov)
- To explore the actual combination of antibodies people have developed, a team led by Drs. Bryan Briney and Dennis R. Burton at Scripps Research examined antibody-producing B cells isolated from blood samples of 10 people between the ages of 18 and 30. (nih.gov)
- Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells' evolutionary and ecological dynamics. (royalsocietypublishing.org)
- The ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the glycan(s) present at conserved sites within its Fc region. (wikipedia.org)
-  The ability of antibodies to bind to FcRs helps to direct the appropriate immune response for each different type of foreign object they encounter. (wikipedia.org)
- The antigen-binding site of the antibody has a unique structure that allows it to bind antigen in a highly specific manner. (nature.com)
- One MAb and a subset of human antibodies bind AM specifically, suggesting that this polysaccharide is antigenically distinct and is expressed in human infection. (elsevier.com)
- Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defenses of the virus in the effort to achieve effective antibody-based treatment and prevention," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. (scienceblog.com)
- The ability of trispecific antibodies to bind to three independent targets at once could make them a useful prototype for treatments developed not only for HIV but also for other infectious diseases, autoimmune diseases and cancers, according to the study authors. (scienceblog.com)
- When activated, a B lymphocyte's secreted antibodies enter the blood and other body fluids, where the bind the antigen and help destroy it. (encyclopedia.com)
- HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. (physiciansweekly.com)
- NEW YORK (GenomeWeb) - Twist Bioscience has signed a deal to offer its customers therapeutic antibody design and optimization services using software developed by Distributed Bio, the companies announced today. (genomeweb.com)
- NGS is Accelerating Therapeutic Antibody Discovery - What Lies Beyond? (genomeweb.com)
- Increasingly, therapeutic antibodies are discovered using transgenic animal systems that have been engineered to express human antibodies. (frontiersin.org)
- Affomix Corporation … announced that Kalgene Pharmaceuticals Inc. has signed a commercial agreement to have Affomix utilize its Y2HExpress technology to select antibodies with potential diagnostic and therapeutic utility in breast cancer. (fdanews.com)
Region of the antibody2
- We then consider how a B cell can alter the tail region of the antibody it makes, while keeping the antigen- binding site unchanged. (nih.gov)
- We were surprised and excited to find that B cell survival could be influenced by a non-antigen-binding region of the antibody, specifically the 'elbow' region that connects the antigen-binding regions to the signaling domain. (eurekalert.org)
- A modification of Jeme's theory of antibody production using the concept of clonal selection. (springer.com)
- This study was undertaken to determine the diversity and distribution of clonal groups in a population of intestinal E. coli isolated from the faeces of children from León, Nicaragua, with (n=381) and without (n=145) diarrhoea, between March 2005 and September 2006. (nih.gov)
- Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. (sciencemag.org)
- Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. (physiciansweekly.com)
- Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. (pnas.org)
- Despite advances in elucidating the structure of broadly neutralizing antibodies (BnAbs), approaches to circumvent the great diversity of HIV, this goal is still some years away. (lww.com)
- I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization. (nih.gov)
- 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)
- This dissertation describes several strategies used to create diversity in non-immune antibody libraries. (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)
- 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)
- This chapter focuses on the processes involved in antibody discovery including the various forms of antibody libraries for phage display and panning processes. (intechopen.com)
- Intestinal antibody libraries were obtained from 10 subjects. (mdpi.com)
- Antibody libraries analysis confirmed the anti-TG2 antibodies mucosal production in all ( n = 8) positive subjects. (mdpi.com)
- Scientists at the Scripps Research Institute (TSRI) have described how a single family of antibodies that broadly neutralizes different strains of HIV has evolved remarkably diverse structures to attack a vulnerable site on the virus. (infectioncontroltoday.com)
- In order to investigate the antigenic diversity of the CPCs of B. fragilis strains, we generated and characterized 10 monoclonal antibodies (MAbs) directed to the CPCs of three reference strains. (asm.org)
- A three-pronged antibody made in the laboratory protected monkeys from infection with two strains of SHIV, a monkey form of HIV, better than individual natural antibodies from which the engineered antibody is derived, researchers report in Science today. (scienceblog.com)
- VRC scientists tested this trispecific antibody in an experiment involving monkeys and two strains of SHIV. (scienceblog.com)
- No one has identified the germline antibody that develops into the PGT121 family. (infectioncontroltoday.com)
- Antibodies can also neutralize targets directly by, for example, binding to a part of a pathogen that it needs to cause an infection. (wikidoc.org)
- Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. (ajtmh.org)
- Moreover, the antigen-binding sites of many antibodies can cross-react with a variety of related but different antigenic determinants, making the antibody defense force even more formidable. (nih.gov)
- While the engineering details differ, these platforms share the ability to raise an immune response that is comprised of antibodies with fully human idiotypes. (frontiersin.org)
- Antibodies are an essential component of our immune system, underpinning the effectiveness of both the primary immune response to microbial pathogens and the protective and long-lived immunity against. (bioportfolio.com)