The Relationship Between Antigenic Structure and Immune Specificity

Benjamini, E.; Scibienski, Robert J.; Thompson, Karen

doi:10.1007/978-1-4757-1343-5_1

Cited by 17 publications

(3 citation statements)

References 100 publications

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“…Whereas B cell or antibody specificity has been linked to determinants which can be considered conformational (28,29), i.e., dependent on the native spatial conformation of the protein, a substantial body of evidence suggests that T cells may recognize sequential determinants, namely those which arise from amino acid sequences that exist in a random coil form (20,(30)(31)(32). In this regard, it is germane that in the present studies T-cell stimulation can be • obtained with cytochrome c fragments which display little a-helical conformation in aqueous solution (G. Corradin, unpublished observations) although the same segment of the protein can be seen to be in a helical structure within the context of the native molecule (33).…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Corradin¹,

Chiller²

1979

The Journal of Experimental Medicine

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Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.

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Section: Discussionmentioning

confidence: 99%

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Corradin¹,

Chiller²

1979

The Journal of Experimental Medicine

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“…Thus cross-linking may expose new regions of the proteins, which become antigenic-determinant groups (heterotopes). The observation that modified proteins may direct antibody response against certain determinants not immunogenic on the native protein has ample precedence (Bonavida & Sercarz, 1971;Benjamini et al, 1972). Heterotopes have been shown to be present in lysozyme (Bonavida & Sercarz, 1971; Thompson et al, 1972) and flagellin (Benjamini et al, 1972), as evidenced by carboxymethylation and acetoacetylation of lysosome and flagellin respectively.…”

Section: Discussionmentioning

confidence: 99%

Demonstration of cross-reacting material in Tay–Sachs disease

Srivastava

Ansari

Hawkins

et al. 1979

Biochemical Journal

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Antibodies against placental hexosaminidase A and kidney alpha-subunits were raised in rabbits after cross-linking the antigens with glutaraldehyde. Anti-(alpha(n)-subunit) antiserum (anti-alpha(n)) precipitated hexosaminidase A but not hexosaminidase B, whereas anti-(hexosaminidase A) antiserum precipitated both hexosaminidases A and B. Specific anti-(hexosaminidase A) antiserum was prepared by absorbing antiserum with hexosaminidase B. Both anti-alpha(n) and anti-(hexosaminidase A) antisera precipitated the CR (cross-reacting) material from eight unrelated patients with Tay-Sachs disease. Immunotitration, immunoelectrophoresis, double-immunodiffusion and radial-immunodiffusion techniques were used to demonstrate the presence of CR material. The CR-material-antibody complex was enzymically inactive. Antiserum raised against kidney or placental hexosaminidase A, without cross-linking with glutaraldehyde, failed to precipitate the CR material, implying that treatment of the protein with glutaraldehyde exposes antigenic determinants that are hidden in the native protein. Since anti-(hexosaminidase B) antiserum did not precipitate the CR material during the immunoelectrophoresis of Tay-Sachs liver extracts, it is suggested that altered alpha-subunits do not combine with beta-subunits. By using immunotitration we have demonstrated the competition between the hexosaminidase B-free Tay-Sachs liver extract and hexosaminidase A for the common binding sites on monospecific anti-(cross-linked hexosaminidase A) antiserum. The amount of CR material in the liver samples from seven cases of Tay-Sachs desease was found to be in the same range as theoretically calculated alpha-subunits in normal liver samples. Similar results were obtained by the radial-immunodiffusion studies. The present studies therefore suggest that Tay-Sachs disease is caused by a structural-gene mutation.

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“…Enzyme-specific antibodies have proven to be sensitive and powerful probes for the purpose of elucidating structural and functional characteristics of certain enzymes (1,2). Such antibodies may produce inhibition or stimulation of enzyme activity, may alter certain physical characteristics such as heat stability, or may react with the enzyme without causing detectable changes in enzymatic activity (1).…”

mentioning

confidence: 99%

Effects of an Antibody to a Highly Purified Na ⁺ , K ⁺ -ATPase from Canine Renal Medulla: Separation of the “Holoenzyme Antibody” into Catalytic and Cardiac Glycoside Receptor-Specific Components

McCans¹,

Lane²,

Lindenmayer³

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

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An antiserum was prepared against a highly purified Na+, K+-adenosine triphosphatase (ATP phosphohydrolase, EC 3.6.1.3). Purification and fractionation yielded two globulin components, one of which appears specific for a digitalis glycoside receptor site or binding conformation and the other for a catalytic site or conformation.Enzyme-specific antibodies have proven to be sensitive and powerful probes for the purpose of elucidating structural and functional characteristics of certain enzymes (1, 2). Such antibodies may produce inhibition or stimulation of enzyme activity, may alter certain physical characteristics such as heat stability, or may react with the enzyme without causing detectable changes in enzymatic activity (1).Antisera to Na+, K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) have been produced and their effects upon enzyme function have recently been published (3-7). In the studies thus far reported, antiserum (3,5,6) or an ammonium sulfateprecipitated globulin fraction (4, 7) was employed. Interpretation of the effects of such antibodies upon enzyme function is complex, since antisera against protein macromolecules ordinarily contain numerous antibody populations specific for various portions (antigenic determinants) of the molecule. The observed effects, therefore, are likely to be the result of several antibodies with different or even opposing effects upon the enzyme.The present report describes a procedure whereby antiserum to Na+,K+-ATPase is purified and separated into two fractions containing antibodies with different effects upon catalytic activity of the enzyme and binding of [3H]ouabain to the enzyme. MATERIALS AND METHODS Production of antiserumWhite, New Zealand rabbits were immunized with highly purified Na+,K+-ATPase prepared from canine renal outer medulla by the method of Lane et al. (8). This enzyme preparation consists of two polypeptides in a molar ratio of 1.0 and contains "supporting" lipids. Enzyme (antigen) was suspended in saline and mixed with an equal volume of Freund's (complete) adjuvant to a final antigen concentration of 1 mg/ml. The rabbits received 0.6 ml of this suspension subcutaneously into the toe-pads (0.2 ml in two rear toe-pads, 0.1 ml in two front toe-pads) weekly for 3 weeks, followed by 0.2 ml intramuscularly into each haunch weekly for 4 weeks. Bleeding was commenced 1 week after the haunch injections and was carried out bimonthly. Booster injections of antigen (0.3 ml into each haunch) were administered on the weeks between bleedings. The precipitate was collected by centrifugation at 10,000 X g for 30 min and redissolved in a volume of deionized water equal to 50% of the original volume of serum. The precipitation and resolubilization cycle was repeated three times. The globulin fraction was then dialyzed against 150 mM Trist HCl buffer (pH 7.4) at a rate of 40 volumes/12 hr with eight changes of the dialysate and a total dialysis period of 96 hr.These conditions of dialysis were found adequate for the removal of residual (NH4)2SO4, which was moni...

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The Relationship Between Antigenic Structure and Immune Specificity

Cited by 17 publications

References 100 publications

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Demonstration of cross-reacting material in Tay–Sachs disease

Effects of an Antibody to a Highly Purified Na ⁺ , K ⁺ -ATPase from Canine Renal Medulla: Separation of the “Holoenzyme Antibody” into Catalytic and Cardiac Glycoside Receptor-Specific Components

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The Relationship Between Antigenic Structure and Immune Specificity

Cited by 17 publications

References 100 publications

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Demonstration of cross-reacting material in Tay–Sachs disease

Effects of an Antibody to a Highly Purified Na + , K + -ATPase from Canine Renal Medulla: Separation of the “Holoenzyme Antibody” into Catalytic and Cardiac Glycoside Receptor-Specific Components

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Effects of an Antibody to a Highly Purified Na ⁺ , K ⁺ -ATPase from Canine Renal Medulla: Separation of the “Holoenzyme Antibody” into Catalytic and Cardiac Glycoside Receptor-Specific Components