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 P chain, suggesting a role for this amino acid in Ni2+ binding to MHC. We propose a general model for Ni2+ recognition in which betaHis81 and two amimo acids from the NH2-terminal part of the MHC bound peptide coordinate Ni2+ which then interacts with some portion of the Valpha CDR1 or CDR2 region.