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- Katharina Gamerdinger
- 1Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany
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- Corinne Moulon
- 1Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany
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- David R. Karp
- 3Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, TX 75390
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- Jeroen van Bergen
- 4Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, Netherlands
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- Frits Koning
- 4Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, Netherlands
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- Doris Wild
- 1Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany
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- Ulrike Pflugfelder
- 1Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany
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- Hans Ulrich Weltzien
- 1Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany
説明
<jats:p>In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR–promiscuous VA22/VB17+ TCR is primarily harbored in its α chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR–associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1α, an N-nucleotide–encoded Tyr94 in CDR3α, and a conserved His81 in the HLA-DR β chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR α chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3α-determined TCR amino acids. This new type of TCR–MHC linkage might explain the high frequency of Ni-reactive T cells in the human population.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 197 (10), 1345-1353, 2003-05-19
Rockefeller University Press