A new type of metal recognition by human T cells: Contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel

Katharina Gamerdinger, Corinne Moulon, David R. Karp, Jeroen Van Bergen, Frits Koning, Doris Wild, Ulrike Pflugfelder, Hans Ulrich Weltzien

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1345-1353
Number of pages9
JournalJournal of Experimental Medicine
Volume197
Issue number10
DOIs
StatePublished - May 19 2003

Keywords

  • Antigen presentation
  • Hapten
  • Hypersensitivity
  • Mutation
  • T cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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