Studies on the Sensitization of Animals With Simple Chemical Compounds

Landsteiner, Karl; Somma, August A. Di

doi:10.1084/jem.72.4.361

Cited by 33 publications

(8 citation statements)

References 9 publications

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“…Hapten-protein complex formation is thought to be an important primary step in the development of allergic contact dermatitis. Since the definitive studies of Landsteiner and Jacobs (1935), reactivity of chemical allergens toward nucleophilic amino acid residues on protein has been coupled with sensitization potential (Basketter et al, 1997). This resulted in the hypothesis that binding of chemical allergens to specific loci on protein might be associated with activation of immune cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of p-Phenylenediamine–Albumin Binding Sites and T-Cell Responses to Hapten-Modified Protein

Jenkinson

Jenkins

Aleksić

et al. 2010

Journal of Investigative Dermatology

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Exposure to p-phenylenediamine (PPD) is associated with the development of T-cell-mediated allergic contact dermatitis. The purpose of this study was to define the nature of the interaction of PPD with the protein and the antigenic determinant that stimulates T cells. Mass spectrometry was employed to show that PPD oxidation products bind irreversibly to cysteine (Cys, position 34) in human serum albumin (HSA). A modified tryptic peptide was characterized with an increase in mass of 106 Da, corresponding to the addition of PPD and not to the secondary products of self conjugation. Lymphocytes from 10 PPD-allergic patients, but not tolerant/naive individuals, were stimulated with PPD and PPD-modified HSA. A total of 70 PPD-specific and 10 PPD-HSA-specific CD4+, CD8+, and CD4+CD8+, Th2-secreting T-cell clones were generated from three allergic patients. In total, 40 clones were stimulated with both PPD and PPD-modified HSA. PPD-modified HSA triggered T-cell responses through a classical hapten mechanism involving processing. Presentation of PPD to several clones was dependent on protein complex formation (42 out of 48) and processing (32 out of 68); however, 12% of clones were triggered with PPD directly. These data identify Cys as the single target for PPD-HSA binding, and show that PPD protein adducts are antigenic determinants in patients with contact dermatitis.

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Section: Discussionmentioning

confidence: 99%

Characterization of p-Phenylenediamine–Albumin Binding Sites and T-Cell Responses to Hapten-Modified Protein

Jenkinson

Jenkins

Aleksić

et al. 2010

Journal of Investigative Dermatology

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“…Because of its low molecular weight penicillin can be compared to 2,4dinitrobenzene derivatives or to picric acid as an antigen. Both these materials have been shown capable of eliciting skin sensitivity (13,14). This activity has been correlated with the ability of the dinitrophenyl compounds to react with endogenous proteins (5) and to the production of reactive metabolites from the picric acid.…”

Section: Discussionmentioning

confidence: 97%

The Development of Antibodies to Penicillin in Rabbits

Josephson

1960

The Journal of Experimental Medicine

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Clinical reactions following administration of penicillin have been noted since this antibiotic was first used (1, 2). These side effects are considered to be allergic, and both serological and cutaneous tests (3, 4) confirm the immunological activity of the drug. However, the characteristics of this compound as an antigen have not yet been defined.Because of its low molecular weight, the binding properties of penicillin are important in its allergenic potential, since other compounds of similar size which possess antigenic activity have been shown capable of firmly coupling with large molecules in vitro and in vivo (5). Penicillin and serum albumin combine in a loose association (6), but this type of binding has been demonstrated to be ineffective in making other low molecular weight substances antigenic (7). The important combination has not been determined. Another unresolved question is that of the specificity of the immunological response, including the cross-reactivifies of the various types of penicillin. These two problems, it was felt, could best be investigated in the experimental animal.In this report the production of antibodies to penicillin in the rabbit is described, and data bearing on the binding capacity of penicillin and the specificity of the immunological response are presented. Materials and MethodsImmunization Te~hnifue.--White rabbits of either sex and 2500 gm. at the start of the experiment were fed Purina chow and water ad libltum. Commercial aqueous penicillin G potassium (Lilly and Pfizer) was used for inoculation with complete Fretmd's adjuvant (Difco). Basic immunization procedure extended over a 4 week period. At the start of the 1st week each animal received 100,000 units of penicillin dissolved in 1 ml. of saline and emulsified with an equal volume of adjuvant. One-tenth ml. of the emulsion was injected into each foot-pad, and the balance injected intradermally in sixteen areas over the back. The second and third injections were performed at weekly intervals and consisted of the deposition of a similar quantity of emulsion, subcutaneously, usually in two separated areas. At the start of the 4th week each animal received 0.1 ml. of the emulsion in each foot-pad and 1.6 ml. subcutaneously. All animals were bled prior to the start of the procedure, 7 days after the last injection and at

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“…Thus, Landsteiner & DiSomma (22) found that guinea pigs sensitized to picric acid cross-reacted with its reduction product picram ic acid. They postulated that a metabolic product of picric acid (possibly a quinone) is the reactive intermediate.…”

Section: Levinementioning

confidence: 99%

Immunochemical Mechanisms of Drug Allergy

Levine¹

1966

Annu. Rev. Med.

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Studies on the Sensitization of Animals With Simple Chemical Compounds

Cited by 33 publications

References 9 publications

Characterization of p-Phenylenediamine–Albumin Binding Sites and T-Cell Responses to Hapten-Modified Protein

Characterization of p-Phenylenediamine–Albumin Binding Sites and T-Cell Responses to Hapten-Modified Protein

The Development of Antibodies to Penicillin in Rabbits

Immunochemical Mechanisms of Drug Allergy

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