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TCR Reactivity in Human Nickel Allergy Indicates Contacts with Complementarity-Determining Region 3 but Excludes Superantigen-Like Recognition¹

Jörg Vollmer^2,*,, Hans Ulrich Weltzien^3,* and Corinne Moulon^4,*

^* Max-Planck-Institut für Immunbiologie, Freiburg, Germany; and Fakultät für Biologie, Universität Freiburg, Freiburg, Germany

Nickel is the most common inducer of contact sensitivity in humans. We previously found that overrepresentation of the TCRBV17 element in Ni-induced CD4⁺ T cell lines of Ni-allergic patients relates to the severity of the disease. Amino acid sequences of these ß-chains suggested hypothetical contact points for Ni²⁺ ions in complementarity-determining region (CDR) 1 and CDR3. To specifically address the molecular requirements for Ni recognition by TCR, human TCR - and ß-chains of VB17⁺ Ni-reactive T cell clones were functionally expressed together with the human CD4 coreceptor in a mouse T cell hybridoma. Loss of CD4 revealed complete CD4 independence for one of the TCR studied. Putative TCR/Ni contact points were tested by pairing of TCR chains from different clones, also with different specificity. TCRBV17 chains with different J regions, but similar CDR3 regions, could be functionally exchanged. Larger differences in the CDR3 region were not tolerated. Specific combinations of - and ß-chains were required, excluding a superantigen-like activation by Ni. Mutation of amino acids in CDR1 of TCRBV17 did not affect Ag recognition, superantigen activation, or HLA restriction. In contrast, mutation of Arg⁹⁵ or Asp⁹⁶, conserved in many CDR3B sequences of Ni-specific, VB17⁺ TCR, abrogated Ni recognition. These results define specific amino acids in the CDR3B region of a VB17⁺ TCR to be crucial for human nickel recognition. CD4 independence implies a high affinity of such receptor types for the Ni/MHC complex. This may point to a dominant role of T cells bearing such receptors in the pathology of contact dermatitis.

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