T cell receptor transfection shows non-HLA-restricted recognition of nickel by CD8+ human T cells to be mediated by alphabeta T cell receptors.
CD8+ T cells have been assigned a prominent role in allergic contact dermatitis, including nickel allergy; however, human nickel-reactive T cells of the CD8+ phenotype have largely escaped detailed investigation. Here we characterize two quite unusual nickel-specific cytotoxic T cell clones isolated from the peripheral blood of two nickel-sensitized patients. These clones mediate nickel-specific cytolysis of many human cell lines, independent of the expression of HLA class I, CD1, or HLA class II molecules. Lysis is mediated by the alphabeta T cell receptors and involves the perforin, but not the Fas/Fas ligand pathway. Both antigen receptors lack sequence homology to each other as well as to typical natural killer T cell receptors. A transfectant expressing the rearranged alphabeta T cell receptor derived from one of the T cell clones unequivocally demonstrates that the T cell receptor itself is necessary and sufficient to confer HLA-independent nickel specificity. The independent isolation of these clones from two individuals points to an important role of such cells in the pathology of nickel contact dermatitis.
Moulon
Corinne
C
Max-Planck-Institut für Immunbiologie, Stübeweg 51, D-79108 Freiburg, Germany.
Choleva
Yoanna
Y
Thierse
Hermann-Josef
HJ
Wild
Doris
D
Weltzien
Hans Ulrich
HU
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002999:Clone Cells; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018942:Macrolides; D009532:Nickel / Q000276:immunology* / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013324:Strontium / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014162:Transfection
D000900:Anti-Bacterial Agents; D016827:CD8 Antigens; D004791:Enzyme Inhibitors; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D018942:Macrolides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D009532:Nickel; C036978:concanamycin A; C025700:strontium chloride; D013324:Strontium