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Components of the Ligand for a Ni++ Reactive Human T Cell Clone
2 Max-Planck-Institute für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany
3 Department of Biochemistry and Molecular Genetics, University of Colorado Health Science Center, Denver, CO 80262
4 Department of Pharmacology and Program in Biomolecular Structure, University of Colorado Health Science Center, Denver, CO 80262
Address correspondence to John Kappler, Howard Hughes Medical Institute, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Phone: 303-398-1322; Fax: 303-398-1396; E-mail: kapplerj{at}njc.org
The major histocompatibility complex (MHC) restriction element for a human Ni2+ reactive T cell, ANi-2.3, was identified as DR52c. A series of experiments established that the functional ligand for this T cell was a preformed complex of Ni2+ bound to the combination of DR52c and a specific peptide that was generated in human and mouse B cells, but not in fibroblasts nor other antigen processing–deficient cells. In addition, ANi-2.3 recognition of this complex was dependent on His81 of the MHC ß chain, suggesting a role for this amino acid in Ni2+ binding to MHC. We propose a general model for Ni2+ recognition in which ßHis81 and two amino acids from the NH2-terminal part of the MHC bound peptide coordinate Ni2+ which then interacts with some portion of the V
CDR1 or CDR2 region.
Key Words: hypersensitivity • T cell receptor • antigen presentation • hapten • nickel
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