Selective interaction of Ni with an MHC-bound peptide.
T cells generally recognize foreign antigens as peptides associated with self-molecules encoded by genes of the major histocompatibility complex (MHC). However, T cells which are specific for non-peptidic haptens have been described, in particular in patients with contact sensitivity reactions to metals such as nickel (Ni). Previously, we isolated MHC class II-restricted Ni-specific T cell clones from patients with Ni allergy. The experiments reported here examine the molecular basis for the interaction between Ni and peptide-MHC complexes. We find that Ni alters a T cell response to a peptide and show that Ni interacts with this peptide to alter its antigenicity rather than its ability to bind to MHC molecules. These findings hold implications for a model of hapten recognition by T cells.
Romagnoli
P
P
Pharma Research Technology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Labhardt
A M
AM
Sinigaglia
F
F
D000595:Amino Acid Sequence; D000953:Antigens, Protozoan / Q000276:immunology; D002460:Cell Line; D006241:Haptens; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D015800:Protozoan Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology
D000953:Antigens, Protozoan; D006241:Haptens; D010455:Peptides; D015800:Protozoan Proteins; D013744:Tetanus Toxin; C041595:circumsporozoite protein, Protozoan; D009532:Nickel