Components of the ligand for a Ni++ reactive human T cell clone.
The major histocompatibility complex (MHC) restriction element for a human Ni(2+) 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 Ni(2+) 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 beta chain, suggesting a role for this amino acid in Ni(2+) binding to MHC. We propose a general model for Ni(2+) recognition in which betaHis81 and two amino acids from the NH(2)-terminal part of the MHC bound peptide coordinate Ni(2+) which then interacts with some portion of the Valpha CDR1 or CDR2 region.
Lu
Linh
L
Howard Hughes Medical Institute, Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Vollmer
Jörg
J
Moulon
Corinne
C
Weltzien
Hans Ulrich
HU
Marrack
Philippa
P
Kappler
John
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017951:Antigen Presentation; D001665:Binding Sites; D002460:Cell Line; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D000949:Histocompatibility Antigens Class II; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D046911:Macromolecular Substances; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D006639:Histidine; D009532:Nickel