Components of the Ligand for a Ni⁺⁺ Reactive Human T Cell Clone

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 β chain, suggesting a role for this amino acid in Ni²⁺ binding to MHC. We propose a general model for Ni²⁺ recognition in which βHis81 and two amino acids from the NH₂-terminal part of the MHC bound peptide coordinate Ni²⁺ which then interacts with some portion of the Vα CDR1 or CDR2 region.