Spec. Issue 2006 - Article Summary

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The chemistry of skin allergy

Jean-Pierre Lepoittevin
Université Louis Pasteur Laboratoire de Dermatochimie, Clinique Dermatologique, CHU, Strasbourg, France
Allergic Contact Dermatitis (ACD) is a very common disease resulting from epidermal proteins being chemically modified by haptens.
The processing of such modified proteins by Langerhans cells, the main antigen-presenting cells in the epidermis, generates altered peptides that are subsequently presented, in association with MHC molecules, to naive T-lymphocytes in the lymph nodes. The whole process results in the selection and activation of T-lymphocyte sub-populations with T-cell Receptors (TcR) specific for the chemical modification. Haptens are usually low molecular weight molecules, lipophilic enough to penetrate the epidermis through the stratum corneum, and with a potent chemical reactivity allowing the formation of a covalent link with nucleophilic residues on protein amino acid side chains. For some time it was considered that the more a molecule is able to modify proteins, the better a sensitiser it is, and that a direct relation could be established between the overall chemical reactivity of a molecule and its sensitising potential. Today, it is hypothesised that the sensitising potential of a molecule is related to its chemical reactivity towards a few specific amino acids relevant to the sensitisation process. Haptens can modify proteins by many different mechanisms, from classical nucleophilicelectrophilic reactions to radical reactions. The knowledge of how haptens can modify proteins is the basis for the development of predictive alternative tests aimed at the identification of hazard and potency, such as Structure Activity Relationships (SAR), Quantitative Structure Activity Relationships (QSAR) and peptide reactivity tests.

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