Antibody Structure and Antibody-Antigen Interactions
5 Classes - x, x, x, x, x • IgG exists in 4 SUBclasses: IgGx, IgGx, IgGx, IgGx • IgA also has 2 subclasses, IgAx and IgAx • Molecules are x, consisting of a basic 4 polypeptide unit of 2 identical heavy chains and 2 identical light chains, linked by disulfide bonds • VALENCE = x
5 Classes - IgG, IgM, IgD, IgA, IgE • IgG exists in 4 SUBclasses: IgG1, IgG2, IgG3, IgG4 • IgA also has 2 subclasses, IgA1 and IgA2 • Molecules are SYMMETRICAL, consisting of a basic 4 polypeptide unit of 2 identical heavy chains and 2 identical light chains, linked by disulfide bonds • VALENCE = # of Antigen binding sites
x immunity is the specific response of the immune system to foreign substances or molecules, which are termed antigens. Although the terms are often used interchangeably, strictly speaking, x defines the capacity of a substance to react with and activate the immune system. Thus, x are substances that induce an immune response, and antigens are substances that react specifically with the immune system. All x are antigens, but not all antigens are x.
Adaptive immunity is the specific response of the immune system to foreign substances or molecules, which are termed antigens. Although the terms are often used interchangeably, strictly speaking, immunogenicity defines the capacity of a substance to react with and activate the immune system. Thus, immunogens are substances that induce an immune response, and antigens are substances that react specifically with the immune system. All immunogens are antigens, but not all antigens are immunogens.
Affinity and avidity of antigen-antibody binding: 1. The reaction between an antibody and an antigen is x, but dissociation of the antibody-antigen complex is x, such that the antibody-antigen complex is essentially x under normal conditions. 2. x is a measure of the strength of the interaction between a single antigen epitope and a single antigen binding site (Fab) of an antibody. The interaction follows the Law of Mass Action, which allows the x to be measured experimentally. This calculation holds for a x (univalent interaction) and x, but provides only an approximation for a multivalent antigen. 3. x is a measure of the strength of the binding between a multivalent antibody and a multivalent antigen. IgG, serum IgA, IgD, and IgE each have # antigen binding sites, whereas secretory IgA and IgM have # and # binding sites, respectively. x is dictated by the affinities of the individual interactions, but the avidity is x than simply the sum of the individual affinities.
Affinity and avidity of antigen-antibody binding: 1. The reaction between an antibody and an antigen is reversible, but dissociation of the antibody-antigen complex is slow, such that the antibody-antigen complex is essentially irreversible under normal conditions. 2. Affinity is a measure of the strength of the interaction between a single antigen epitope and a single antigen binding site (Fab) of an antibody. The interaction follows the Law of Mass Action, which allows the affinity to be measured experimentally. This calculation holds for a hapten (univalent interaction) and Fab, but provides only an approximation for a multivalent antigen. 3. Avidity is a measure of the strength of the binding between a multivalent antibody and a multivalent antigen. IgG, serum IgA, IgD, and IgE each have two antigen binding sites, whereas secretory IgA and IgM have four and ten binding sites, respectively. Avidity is dictated by the affinities of the individual interactions, but the avidity is greater than simply the sum of the individual affinities.
All immunoglobulins are x, but the amount of x varies with the immunoglobulin. Most of the oligosacchrides are attached to the x domains of the heavy chain. The carbohydrate may play a role in immunoglobulin secretion by x cells.
All immunoglobulins are glycoproteins, but the amount of carbohydrate varies with the immunoglobulin. Most of the oligosacchrides are attached to the constant domains of the heavy chain. The carbohydrate may play a role in immunoglobulin secretion by plasma cells.
x defines small structural variations in the constant region of the heavy and light chains of an immunoglobulin of the same isotype within the same species. The genes encoding heavy chains (most notably those of IgG) and light chains are x. The structural variations encoded by the different alleles result from the substitution in many cases of only one or two amino acids. The number of x for human IgG ranges from 0 for IgG4 to 19 for IgG3. x exhibit Mendelian form of inheritance.
Allotype defines small structural variations in the constant region of the heavy and light chains of an immunoglobulin of the same isotype within the same species. The genes encoding heavy chains (most notably those of IgG) and light chains are polymorphic. The structural variations encoded by the different alleles result from the substitution in many cases of only one or two amino acids. The number of allotypes for human IgG ranges from 0 for IgG4 to 19 for IgG3. Allotypes exhibit Mendelian form of inheritance.
Antibodies are protein molecules that comprise one arm (humoral) of the x immune response. The antibodies recognize and bind to foreign substances (antigens) encountered in the environment. The antibody proteins are also referred to as x, which are a heterogeneous group of glycoproteins that constitute approximately 20% of total plasma proteins. Antibodies are present free in the x and on x-lymphocytes.
Antibodies are protein molecules that comprise one arm (humoral) of the adaptive immune response. The antibodies recognize and bind to foreign substances (antigens) encountered in the environment. The antibody proteins are also referred to as immunoglobulins, which are a heterogeneous group of glycoproteins that constitute approximately 20% of total plasma proteins. Antibodies are present free in the circulation and on B-lymphocytes.
Antigen-antibody complexes are also referred to as x. The form taken by the antigen-antibody complex depends on the x of the antigen and the x of the antigen and antibody concentrations. Antibody interactions with particulate antigens (such as intact cells) results in x of the cells, whereas binding of antibody to soluble antigens forms immune complexes that may x. The formation of a x is a function of the antigen and antibody concentrations.
Antigen-antibody complexes are also referred to as immune complexes. The form taken by the antigen-antibody complex depends on the nature of the antigen and the ratio of the antigen and antibody concentrations. Antibody interactions with particulate antigens (such as intact cells) results in agglutination of the cells, whereas binding of antibody to soluble antigens forms immune complexes that may precipitate. The formation of a precipitate is a function of the antigen and antibody concentrations.
Antigenic Determinants: Only limited portions of antigenic molecules interact with an antibody. These areas are termed x or x. The number of distinct antigenic determinants varies with x and x of the molecule. However, a given individual may respond to only a subset of determinants. Epitopes that induce an antibody response in the majority of individuals are termed x epitopes.
Antigenic Determinants: Only limited portions of antigenic molecules interact with an antibody. These areas are termed antigenic determinants or epitopes. The number of distinct antigenic determinants varies with size and complexity of the molecule. However, a given individual may respond to only a subset of determinants. Epitopes that induce an antibody response in the majority of individuals are termed immunodominant epitopes.
Antigenic determinants are usually 5-7x for proteins or 5-7 x or x. Thus, they have similar molecular dimensions. In general, the antigenic determinants for antibody interactions are on the most exposed (x) regions of a molecule.
Antigenic determinants are usually 5-7 amino acids for proteins or 5-7 monosaccharides or polysaccharides. Thus, they have similar molecular dimensions. In general, the antigenic determinants for antibody interactions are on the most exposed (hydrophilic) regions of a molecule.
Antigens arise from both x and x sources. x-derived antigens may be soluble molecules such as bacterial toxins, or components of more complex structures such as bacteria or viruses. x-derived antigens are expressed on the cell surface of virus-infected cells or tumor cells. Antigens may be: proteins (toxins, allergens, viral proteins, etc); polysaccharides (bacterial cell walls and ABO blood group antigens); lipids; organic molecules; inorganic molecules, and nucleoproteins.
Antigens arise from both external and internal sources. Externally-derived antigens may be soluble molecules such as bacterial toxins, or components of more complex structures such as bacteria or viruses. Endogenously-derived antigens are expressed on the cell surface of virus-infected cells or tumor cells. Antigens may be: proteins (toxins, allergens, viral proteins, etc); polysaccharides (bacterial cell walls and ABO blood group antigens); lipids; organic molecules; inorganic molecules, and nucleoproteins.
x and x are each important to the antigenicity of proteins and polysaccharides. Thus, a conformational determinant is based on the overall x of a substance, e.g., globular versus helical. In contract, a specific sequence of x or x defines a sequential determinant. The sequences may be either x or x, but the sequences are almost always localized in x regions of the molecule. Denaturation of the antigenic molecule destroys a x determinant, but not a x determinant. In some cases, denaturation may uncover a new x determinant that is not accessible in the native molecule.
Conformation and sequence are each important to the antigenicity of proteins and polysaccharides. Thus, a conformational determinant is based on the overall structure of a substance, e.g., globular versus helical. In contract, a specific sequence of amino acids or monosaccharides defines a sequential determinant. The sequences may be either terminal or internal, but the sequences are almost always localized in hydrophilic regions of the molecule. Denaturation of the antigenic molecule destroys a conformational determinant, but not a sequential determinant. In some cases, denaturation may uncover a new sequential determinant that is not accessible in the native molecule.
Criteria for immunogenicity: 1. x. The immune system is set up to distinguish self from non-self. With limited exceptions, only x (non-self) molecules are immunogenic. 2. Molecular x. A minimum x is necessary, but there is no specific x threshold. In general, molecules <x kD are x immunogenic, if at all, whereas molecules >x kD are x immunogenic. 3. Chemical x. Immunogenicity increases with x. x of a single amino acid are poor immunogens, whereas polymers of repeating units of 2 or 3 amino acids may be x immunogenic.
Criteria for immunogenicity: 1. Foreign. The immune system is set up to distinguish self from non-self. With limited exceptions, only foreign (non-self) molecules are immunogenic. 2. Molecular size. A minimum size is necessary, but there is no specific size threshold. In general, molecules <5 kD are weakly immunogenic, if at all, whereas molecules >100 kD are strongly immunogenic. 3. Chemical complexity. Immunogenicity increases with complexity. Homopolymers of a single amino acid are poor immunogens, whereas polymers of repeating units of 2 or 3 amino acids may be very immunogenic.
Each polypeptide chain contains x, which are compact globular regions containing # amino acids and are formed by intra-chain x bonds. Light chains contain # domains, and heavy chains contain # or # domains.
Each polypeptide chain contains domains, which are compact globular regions containing 100-110 amino acids and are formed by intra-chain disulfide bonds. Light chains contain two domains, and heavy chains contain four or five domains.
x are small, chemically defined molecules that are not immunogenic but that can react with antibody of appropriate specificity. Thus, x are the one class of substances that are antigens but not immunogens. Haptogens are always x molecules, (i.e., have a single epitope) in contrast to multivalent proteins or polysaccharides. Haptens (e.g., dinitrophenol, DNP) act as a x or x antigenic determinant when coupled to a protein x. The protein carrier has its own inherent antigenic determinants. Some antibodies made against the x-x complex will be specific for the hapten. Virtually any chemical structure may act as a hapten if x to a protein carrier.
Haptens are small, chemically defined molecules that are not immunogenic but that can react with antibody of appropriate specificity. Thus, haptens are the one class of substances that are antigens but not immunogens. Haptens are always univalent molecules, (i.e., have a single epitope) in contrast to multivalent proteins or polysaccharides. Haptens (e.g., dinitrophenol, DNP) act as a partial or complete antigenic determinant when coupled to a protein carrier. The protein carrier has its own inherent antigenic determinants. Some antibodies made against the hapten-carrier complex will be specific for the hapten. Virtually any chemical structure may act as a hapten if coupled to a protein carrier.
Heavy chains vary in size from approximately 50 kD to 75 kD and are divided into five classes: x, x, x, x, x. The five classes differ structurally in their x domains, and it is the structure in the x domain that determines the class of the antibody chain, as well as its biological function.
Heavy chains vary in size from approximately 50 kD to 75 kD and are divided into five classes: gamma; alpha; mu; delta; and epsilon. The five classes differ structurally in their constant domains, and it is the structure in the constant domain that determines the class of the antibody chain, as well as its biological function.
x is determined by structural differences within the variable domains of heavy and light chains. Each clone of antibody-producing lymphocytes synthesizes an immunoglobulin molecule with a unique x region amino acid sequence. This x dictates the antigen specificity of the antibody.
Idiotype is determined by structural differences within the variable domains of heavy and light chains. Each clone of antibody-producing lymphocytes synthesizes an immunoglobulin molecule with a unique variable region amino acid sequence. This sequence dictates the antigen specificity of the antibody.
x is present in serum and is the predominant antibody in seromucous secretions.
IgA is present in serum and is the predominant antibody in seromucous secretions.
IgA is present in serum and is the predominant antibody in x secretions. Serum IgA constitutes x% of serum immunoglobulin and exists largely (>80%) in a monomeric structure analogous to x. Serum IgA also forms dimers (20%). The heavy chain is of the alpha class, and there are two subclasses of IgA: IgAx and IgAx. Secretory IgA is present almost exclusively in x and exists primarily as a x (385 kD). The two monomers are linked covalently by a x chain (same as for IgM). Each secretory IgA molecule also contains a x component, which is a 70 kD polypeptide fragment of a receptor for polymeric immunoglobulin on the basal surface of x cells. The secretory component (or piece) facilitates transport of the secretory IgA across the x into the lumen and protects the secretory IgA from proteolysis. Secretory IgA is responsible for immunity at x surfaces.
IgA is present in serum and is the predominant antibody in seromucous secretions. Serum IgA constitutes 15-20% of serum immunoglobulin and exists largely (>80%) in a monomeric structure analogous to IgG. Serum IgA also forms dimers (20%). The heavy chain is of the alpha class, and there are two subclasses of IgA: IgA1 and IgA2. Secretory IgA is present almost exclusively in seromucous secretions and exists primarily as a dimer (385 kD). The two monomers are linked covalently by a J chain (same as for IgM). Each secretory IgA molecule also contains a secretory component, which is a 70 kD polypeptide fragment of a receptor for polymeric immunoglobulin on the basal surface of mucosal epithelial cells. The secretory component (or piece) facilitates transport of the secretory IgA across the mucosal epithelium into the lumen and protects the secretory IgA from proteolysis. Secretory IgA is responsible for immunity at mucosal surfaces.
IgD is a monomer (delta heavy chain) of x kD. It is the predominant immunoglobulin, with IgM, on mature x lymphocytes, but comprises x% of total serum immunoglobulin. Like IgM, IgD can mediate x cell activation.
IgD is a monomer (delta heavy chain) of 184 kD. It is the predominant immunoglobulin, with IgM, on mature B lymphocytes, but comprises <1% of total serum immunoglobulin. Like IgM, IgD can mediate B cell activation.
x is a monomer (delta heavy chain) of 184 kD. It is the predominant immunoglobulin, with IgM, on mature B lymphocytes, but comprises <1% of total serum immunoglobulin. Like IgM, x can mediate B cell activation.
IgD is a monomer (delta heavy chain) of 184 kD. It is the predominant immunoglobulin, with IgM, on mature B lymphocytes, but comprises <1% of total serum immunoglobulin. Like IgM, IgD can mediate B cell activation.
IgE is a monomer (epsilon heavy chain) of x kD. The x heavy chain contains an additional constant domain. IgE comprises <0.004% of total serum immunoglobulin, but binds strongly to x receptors for IgE on x and x cells. IgE triggers x release from mast cells and basophils, aiding in host defense against x parasites. IgE also mediates immediate x reactions.
IgE is a monomer (epsilon heavy chain) of 180 kD. The epsilon heavy chain contains an additional constant domain. IgE comprises <0.004% of total serum immunoglobulin, but binds strongly to Fc receptors for IgE on basophils and mast cells. IgE triggers granule release from mast cells and basophils, aiding in host defense against metazoan (worm) parasites. IgE also mediates immediate hypersensitivity reactions.
x triggers granule release from mast cells and basophils, aiding in host defense against metazoan (worm) parasites. x also mediates immediate hypersensitivity reactions.
IgE triggers granule release from mast cells and basophils, aiding in host defense against metazoan (worm) parasites. IgE also mediates immediate hypersensitivity reactions.
IgG constitutes x% of total serum immunoglobulin in adults. The IgG molecule (146 kD) is a monomer comprised of two (gamma) heavy chains and two light chains. Four subclasses of IgG (relative abundance: IgGx>> IgGx>IgGx>IgGx) are defined by differences in their constant regions. It is the major antibody formed during the x immune response and the only antibody able to cross the x (all subclasses). Thus, IgG provides immunity in x. The IgG subclasses 1-3 activate x, are x (molecules that mediate the binding of particles to phagocytes), and mediate x (ADCC; an effector mechanism of cell-mediated immunity). In addition, IgG1 and IgG3 bind in monomeric form to x receptors for IgG on monocytes and macrophages. IgG4 is unique in that one IgG4 molecule can exchange one heavy chain and one light chain module (i.e., one half of the antibody molecule) with a heavy chain and light chain module of a second IgG4 molecule. Thus, most IgG4 molecules recognize # different antigens, making it functionally monovalent.
IgG constitutes 75% of total serum immunoglobulin in adults. The IgG molecule (146 kD) is a monomer comprised of two (gamma) heavy chains and two light chains. Four subclasses of IgG (relative abundance: IgG1>> IgG2>IgG3>IgG4) are defined by differences in their constant regions. It is the major antibody formed during the secondary immune response and the only antibody able to cross the placenta (all subclasses). Thus, IgG provides immunity in newborns. The IgG subclasses 1-3 activate complement, are opsonins (molecules that mediate the binding of particles to phagocytes), and mediate Antibody-Dependent Cellular Cytotoxicity (ADCC; an effector mechanism of cell-mediated immunity). In addition, IgG1 and IgG3 bind in monomeric form to Fc receptors for IgG on monocytes and macrophages. IgG4 is unique in that one IgG4 molecule can exchange one heavy chain and one light chain module (i.e., one half of the antibody molecule) with a heavy chain and light chain module of a second IgG4 molecule. Thus, most IgG4 molecules recognize two different antigens, making it functionally monovalent.
x is the major antibody formed during the secondary immune response and the only antibody able to cross the placenta (all subclasses). Thus, x provides immunity in newborns.
IgG is the major antibody formed during the secondary immune response and the only antibody able to cross the placenta (all subclasses). Thus, IgG provides immunity in newborns.
x, x, or x are present on the surface of x B lymphocytes, where they serve as antigen receptors. The membrane-bound form of x is a monomer. The membrane form of the antibodies are anchored by a hydrophobic (lipophilic) segment at the x-terminus of the heavy chain that arises from alternative x splicing of the heavy chain message.
IgG, IgA, or IgE are present on the surface of memory B lymphocytes, where they serve as antigen receptors. The membrane-bound form of IgA is a monomer. The membrane form of the antibodies are anchored by a hydrophobic (lipophilic) segment at the carboxy-terminus of the heavy chain that arises from alternative RNA splicing of the heavy chain message.
IgM constitutes x% of serum immunoglobulin and has a pentameric structure of x kD. Each of the five monomer subunits is identical and contains two (mu) heavy chains and two light chains. The heavy chain contains an additional domain; therefore, the size of the mu heavy chain is about 65 kD (110 amino acids) larger than the gamma heavy chain. The monomer subunits are linked by x bonds between adjacent CHx and CHx domains, and the pentamer is closed by the x chain, a 15 kD glycoprotein that covalently links (via disulfide bonds) two monomer subunits together. IgM is the major antibody class formed in the x immune response, is the most efficient activator of x, and is expressed on x lymphocytes, where it mediates antigen-specific x-lymphocyte activation. On x lymphocyte surfaces, IgM is found as a monomer, and it is the antigen receptor for the x cell.
IgM constitutes 10% of serum immunoglobulin and has a pentameric structure of 970 kD. Each of the five monomer subunits is identical and contains two (mu) heavy chains and two light chains. The heavy chain contains an additional domain; therefore, the size of the mu heavy chain is about 65 kD (110 amino acids) larger than the gamma heavy chain. The monomer subunits are linked by disulfide bonds between adjacent CH3 and CH4 domains, and the pentamer is closed by the J chain, a 15 kD glycoprotein that covalently links (via disulfide bonds) two monomer subunits together. IgM is the major antibody class formed in the primary immune response, is the most efficient activator of complement, and is expressed on B lymphocytes, where it mediates antigen-specific B-lymphocyte activation. On B lymphocyte surfaces, IgM is found as a monomer, and it is the antigen receptor for the B cell.
x is the major antibody class formed in the primary immune response, is the most efficient activator of complement, and is expressed on B lymphocytes, where it mediates antigen-specific B-lymphocyte activation. On B lymphocyte surfaces, IgM is found as a monomer, and it is the antigen receptor for the B cell.
IgM is the major antibody class formed in the primary immune response, is the most efficient activator of complement, and is expressed on B lymphocytes, where it mediates antigen-specific B-lymphocyte activation. On B lymphocyte surfaces, IgM is found as a monomer, and it is the antigen receptor for the B cell.
Immunoglobulins possess a x-sensitive region between the x and x constant domains of the heavy chain (CH1 and CH2). This region is more exposed than other portions of the immunoglobulin molecule and is also more flexible. Hence, the region is termed the x region. The enzyme x acts in this region to cleave the antibody molecule into two x (Fragment, antigen-binding) fragments and one x (Fragment, constant) fragment. Each Fab fragment is composed of a light chain and the x and x constant domains of the heavy chain. Each Fab fragment contains x antigen-binding site. The Fc fragment is composed of the x-terminal portion of the heavy chains and initiates biological activities subsequent to antigen binding. A second enzyme, x, acts at the hinge region to cleave the antibody molecule into one x fragment and a degraded x fragment. Each F(ab')2 contains two covalently-linked Fab pieces and consequently is x (i.e., contains two antigen binding sites).
Immunoglobulins possess a protease-sensitive region between the first and second constant domains of the heavy chain (CH1 and CH2). This region is more exposed than other portions of the immunoglobulin molecule and is also more flexible. Hence, the region is termed the hinge region. The enzyme papain acts in this region to cleave the antibody molecule into two Fab (Fragment, antigen-binding) fragments and one Fc (Fragment, constant) fragment. Each Fab fragment is composed of a light chain and the variable and first constant domains of the heavy chain. Each Fab fragment contains one antigen-binding site. The Fc fragment is composed of the carboxy-terminal portion of the heavy chains and initiates biological activities subsequent to antigen binding. A second enzyme, pepsin, acts at the hinge region to cleave the antibody molecule into one F(ab')2 fragment and a degraded Fc fragment. Each F(ab')2 contains two covalently-linked Fab pieces and consequently is bivalent (i.e., contains two antigen binding sites).
In antibody excess, the concentration of x is in excess relative to the concentration of x. Consequently, most of the x is bound in a univalent fashion to x. In antigen excess, the concentration of x is in excess relative to that of the x. Ultimately, one x molecule will bind and cross-link two x molecules. At equivalence, the relative concentrations of x and x are equivalent. Antibody such as IgG binds x and ultimately can form an x with a multivalent antigen. An antigen must be at least bivalent for an insoluble lattice and, thus, a x, to form. Other factors, such as number and heterogeneity of antigenic determinants, amount and heterogeneity of antibody, and antibody affinity, also influence lattice formation.
In antibody excess, the concentration of antibody is in excess relative to the concentration of antigen. Consequently, most of the antibody is bound in a univalent fashion to antigen. In antigen excess, the concentration of antigen is in excess relative to that of the antibody. Ultimately, one antibody molecule will bind and cross-link two antigen molecules. At equivalence, the relative concentrations of antigen and antibody are equivalent. Antibody such as IgG binds bivalently and ultimately can form an insoluble lattice with a multivalent antigen. An antigen must be at least bivalent for an insoluble lattice and, thus, a precipitate, to form. Other factors, such as number and heterogeneity of antigenic determinants, amount and heterogeneity of antibody, and antibody affinity, also influence lattice formation.
In x, the concentration of antibody is in excess relative to the concentration of antigen. Consequently, most of the antibody is bound in a univalent fashion to antigen. In x, the concentration of antigen is in excess relative to that of the antibody. Ultimately, one antibody molecule will bind and cross-link two antigen molecules. At x, the relative concentrations of antigen and antibody are equivalent. Antibody such as IgG binds bivalently and ultimately can form an insoluble lattice with a multivalent antigen. An antigen must be at least bivalent for an insoluble lattice and, thus, a precipitate, to form. Other factors, such as number and heterogeneity of antigenic determinants, amount and heterogeneity of antibody, and antibody affinity, also influence lattice formation.
In antibody excess, the concentration of antibody is in excess relative to the concentration of antigen. Consequently, most of the antibody is bound in a univalent fashion to antigen. In antigen excess, the concentration of antigen is in excess relative to that of the antibody. Ultimately, one antibody molecule will bind and cross-link two antigen molecules. At equivalence, the relative concentrations of antigen and antibody are equivalent. Antibody such as IgG binds bivalently and ultimately can form an insoluble lattice with a multivalent antigen. An antigen must be at least bivalent for an insoluble lattice and, thus, a precipitate, to form. Other factors, such as number and heterogeneity of antigenic determinants, amount and heterogeneity of antibody, and antibody affinity, also influence lattice formation.
x defines the structural differences in the constant regions that distinguish the class and subclasses of heavy chains and the class of light chains within a single species. Each x is encoded by a specific gene.
Isotype defines the structural differences in the constant regions that distinguish the class and subclasses of heavy chains and the class of light chains within a single species. Each isotype is encoded by a specific gene.
x proteins are immunoglobulins synthesized by a single clone of a malignant x cell. Therefore, a myeloma protein is x (i.e. derived from a single clone) and has been observed with all immunoglobulin classes. Free light chains termed x proteins are found in the urine of patients with multiple myeloma.
Myeloma proteins are immunoglobulins synthesized by a single clone of a malignant plasma cell. Therefore, a myeloma protein is monoclonal (i.e. derived from a single clone) and has been observed with all immunoglobulin classes. Free light chains termed Bence-Jones proteins are found in the urine of patients with multiple myeloma.
Precipitation of an x can be observed when increasing amounts of an antigen are added to a series of test tubes, each containing a constant amount of antibody. As the amount of antigen added increases, the amount of precipitate x and then x. Three zones of precipitation can be distinguished: what are they?
Precipitation of an immune complex can be observed when increasing amounts of an antigen are added to a series of test tubes, each containing a constant amount of antibody. As the amount of antigen added increases, the amount of precipitate increases and then decreases. Three zones of precipitation can be distinguished: antibody excess; equivalence; and antigen excess.
Similar changes in immune complex size are also observed clinically. In the initial stage following antigen exposure, x dominates until sufficient antibody is produced. The complexes remain x and are not cleared from the circulation. However, the complexes, due to their larger size, can become x in the tissues and eventually can cause tissue x. As more x is produced following antigen exposure, x and x are achieved. x cells in the reticuloendothelial system clear these larger immune complexes from the blood via recognition of the x portions of the antibody molecules. The larger immune complexes can also activate x and x cells in the circulation via the x region. Thus, in conditions where x exposure persists, such as in autoimmune diseases, formation of the immune complexes can overwhelm the x system and lead to tissue x.
Similar changes in immune complex size are also observed clinically. In the initial stage following antigen exposure, antigen excess dominates until sufficient antibody is produced. The complexes remain soluble and are not cleared from the circulation. However, the complexes, due to their larger size, can become trapped in the tissues and eventually can cause tissue damage. As more antibody is produced following antigen exposure, equivalence and antibody excess are achieved. Phagocytic cells in the reticuloendothelial system clear these larger immune complexes from the blood via recognition of the Fc portions of the antibody molecules. The larger immune complexes can also activate complement and phagocytic cells in the circulation via the Fc region. Thus, in conditions where antigen exposure persists, such as in autoimmune diseases, formation of the immune complexes can overwhelm the reticuloendothelial system and lead to tissue damage.
Studies using haptens have shown that antibodies react very specifically with the antigenic determinant that x the antibody formation. However, antibodies made against one antigen or hapten may, in some cases, react with another antigen or hapten. This phenomenon is termed x and reflects shared antigenic determinants by the two antigens. Generally, an antibody binds x strongly to a cross-reacting antigen than to the antigen that induced the antibody formation.
Studies using haptens have shown that antibodies react very specifically with the antigenic determinant that induced the antibody formation. However, antibodies made against one antigen or hapten may, in some cases, react with another antigen or hapten. This phenomenon is termed cross-reactivity and reflects shared antigenic determinants by the two antigens. Generally, an antibody binds less strongly to a cross-reacting antigen than to the antigen that induced the antibody formation.
The x-terminal domain of each heavy and light chain displays more x in amino acid sequence than the other domains. Accordingly, the N-terminal domain of each polypeptide chain is designated as the x domain (or region), and the remaining domains are designated as x domains (or regions). The x regions exhibit little variation in amino acid sequence and have very similar secondary and tertiary structures.
The N-terminal domain of each heavy and light chain displays more variation in amino acid sequence than the other domains. Accordingly, the N-terminal domain of each polypeptide chain is designated as the variable domain (or region), and the remaining domains are designated as constant domains (or regions). The constant regions exhibit little variation in amino acid sequence and have very similar secondary and tertiary structures.
The amino acids in the hypervariable regions interact with the amino acids or monosaccharides that comprise the antigenic determinants. Therefore, the molecular dimensions of the antigenic determinant and the antigen binding site must be x to each other. (For this reason, the hypervariable region is sometimes referred to as the x region.) The strong association between antigen and antibody is the result of multiple x bonds (e.g., hydrogen, Vander Waal, and electrostatic) formed between the antigen binding site and the antigenic determinant. x is necessary for a close fit, because the strength of the x bonds is inversely related to the x between the interacting groups.
The amino acids in the hypervariable regions interact with the amino acids or monosaccharides that comprise the antigenic determinants. Therefore, the molecular dimensions of the antigenic determinant and the antigen binding site must be complementary to each other. (For this reason, the hypervariable region is sometimes referred to as the complementarity-determining region.) The strong association between antigen and antibody is the result of multiple non-covalent bonds (e.g., hydrogen, Vander Waal, and electrostatic) formed between the antigen binding site and the antigenic determinant. Complementarity is necessary for a close fit, because the strength of the non-covalent bonds is inversely related to the distance between the interacting groups.
The antigen binding site of an antibody is formed by the x domains of the heavy and light chains. The variability in the amino acid sequence in the variable domain, however, is/is not uniformly distributed throughout the domains. Regions that show the greatest variability are termed the x regions, whereas the relatively more constant sequences between the x sequences are termed the x regions. Light chains have # hypervariable regions, and heavy chains have # hypervariable regions. A specific variable domain may be linked to any x domain of a heavy chain class.
The antigen binding site of an antibody is formed by the variable domains of the heavy and light chains. The variability in the amino acid sequence in the variable domain, however, is not uniformly distributed throughout the domains. Regions that show the greatest variability are termed the hypervariable regions, whereas the relatively more constant sequences between the hypervariable sequences are termed the framework regions. Light chains have three hypervariable regions, and heavy chains have three or four hypervariable regions. A specific variable domain may be linked to any constant domain of a heavy chain class.
The basic structure of an antibody is comprised of # polypeptide chains: # identical x chains and # identical x chains. Together, this basic unit is termed a x. As the names imply, the heavy chain (x kD) is approximately twice the size of the light chain (x kD). The chains are linked together by x bonds as well as by non-x bonds in a bilaterally symmetrical arrangement. (There is one exception to this rule.)
The basic structure of an antibody is comprised of four polypeptide chains: two identical heavy chains and two identical light chains. Together, this basic unit is termed a monomer. As the names imply, the heavy chain (50-65 kD) is approximately twice the size of the light chain (25 kD). The chains are linked together by covalent disulfide bonds as well as by non-covalent bonds in a bilaterally symmetrical arrangement. (There is one exception to this rule.)
The x domains (i.e., the variable or constant domains) of the heavy and light chains are paired in the Fab. More precisely, the variable domains of the heavy and light chains are aligned to bring together the x regions of each chain. It is the hypervariable regions of the heavy and light chains together that form the x. The framework regions are important in the folding and proper orientation of the x site.
The homologous domains (i.e., the variable or constant domains) of the heavy and light chains are paired in the Fab. More precisely, the variable domains of the heavy and light chains are aligned to bring together the hypervariable regions of each chain. It is the hypervariable regions of the heavy and light chains together that form the antigen binding site. The framework regions are important in the folding and proper orientation of the binding site.
There are two classes of light chains, x and x. Both are approximately 25 kD in size, but they differ structurally in the x domain. Both types of light chains display an equal ability to associate with heavy chains, although the ratio of kappa to lambda light chains in human immunoglobulins is approximately x. However, one immunoglobulin molecule contains # identical kappa or # identical lambda chains.
There are two classes of light chains, kappa and lambda. Both are approximately 25 kD in size, but they differ structurally in the constant domain. Both types of light chains display an equal ability to associate with heavy chains, although the ratio of kappa to lambda light chains in human immunoglobulins is approximately 2:1. However, one immunoglobulin molecule contains two identical kappa or two identical lambda chains.