부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tox.2004.12.015 Byline: Hermann-Josef Thierse (a)(b), Katharina Gamerdinger (a), Christof Junkes (a), Nelson Guerreiro (c), Hans Ulrich Weltzien (a) Keywords: Nickel; Hypersensitivity; T lymphocyte; Albumin; Heat shock; Protein Abstract: Haptens are classified as low molecular chemicals with an intrinsic potential to covalently modify proteins, and many of them are strong inducers of contact hypersensitivity (CHS). CHS is T cell mediated, and hapten-specific T cells have been shown to interact with hapten-modified, MHC-associated peptides. However, the most common contact sensitizer in the industrialized world is nickel. In contrast to classical haptens, nickel ions do not form covalent bonds to proteins, but rather become caught in reversible coordination complexes. We here review work demonstrating that some T cells, indeed, may react to such Ni complexes on the MHC/peptide-surface absolutely comparable to other haptens. In other cases, Ni ions unlike classical haptens, may activate T cells by crosslinking their receptors to MHC molecules, independent of the nature of the associated peptide. Moreover, Ni-interacting proteins appear to make use of the reversibility of Ni-binding, and to mediate the transfer of Ni-ions to the receptor-MHC interphase. We have demonstrated such properties for human serum albumin (HSA) as well as for transferrin and identified numerous new Ni-binding proteins in human B-cell lines or dendritic cells by affinity purification and mass spectroscopy. These proteins include a notable number of known heat shock proteins and chaperones, implying that Ni may functionally interfere with these stress proteins. Author Affiliation: (a) Max-Planck-Institut fur Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany (b) Lehrstuhl fur Molekulare Immunologie der Albert-Ludwigs-Universitat, Stubeweg 51, D-79108 Freiburg, Germany (c) Novartis Pharma AG, Basel, Switzerland