International Immunology, Vol. 12, No. 12, 1723-1731,
December 2000
© 2000 Japanese Society for Immunology
Antigen contacts by Ni-reactive TCR: typical 
ß chain cooperation versus chain-dominated specificity
1 Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany
2 Fakultät für Biologie, Universität Freiburg, Schänzlstr. 1, D-79104 Freiburg, Germany
Correspondence to: H. U. Weltzien
VB17+ TCR dominate in Ni-driven T cell cultures from highly Ni-sensitized patients. Using transfection of TCR from three CD4+, VB17+, Ni-specific human T cell clones, we studied their Ni–MHC contacts by site-directed TCR mutation and combination of 
and ß chains between different TCR. All three TCR exhibited N-nucleotide-determined Arg–Asp motifs in their CDR3-ß sequences. Two of them were specifically restricted to HLA-DR13, while the third one accepted a variety of HLA-DR alleles. The highly similar or ß chains of the DR13-restricted TCR were interchangable without loss of specificity, but or ß chains of other TCR were not tolerated. Mutations of their Arg–Asp motif revealed loss of reactivity upon exchanging Asp for Glu or Ala and of Arg for Ala but not of Arg for Lys or the Ni binding His. Reactivity was also destroyed by mutation of chain position 51, proposed as a general contact site for MHC. Hence, in these two TCR the Arg–Asp motif is clearly involved in contacting Ni–MHC complexes, and close cooperation between and ß chain is required. In contrast, the third TCR retained Ni reactivity upon mutation of chain position 51 or of its ß chain Arg–Asp motif, which rather affected the pattern of DR cross-restriction. Moreover, its chain paired with various ß chains from other, even mouse TCR, irrespective of their specificity, retaining Ni reactivity as well as promiscuous HLA-DR restriction. This preponderance of an chain in defining specificity indicates fundamental differences in Ni interactions of individual TCR and implies that ß chain similarities may not necessarily result from antigen selection.
Keywords: allergy, antigen binding, human, metal, TCR
3 Present address: CpG Immuno Pharmaceuticals GmbH, Max-Volmer-Strasse 4, 40724 Hilden, Germany
4 Present address: Pfizer Laboratories, 3–9 Rue de la Loge, BP100, 94265 Fresnes Cedex, France
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