T cell receptor transfection shows non-HLA-restricted recognition of nickel by CD8+ human T cells to be mediated by alphabeta T cell receptors

J Invest Dermatol. 2003 Sep;121(3):496-501. doi: 10.1046/j.1523-1747.2003.12405.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • Dermatitis, Allergic Contact / immunology*
  • Enzyme Inhibitors / pharmacology
  • Epitopes
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Macrolides*
  • Nickel / immunology*
  • Nickel / pharmacology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Strontium / pharmacology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection

Substances

  • Anti-Bacterial Agents
  • CD8 Antigens
  • Enzyme Inhibitors
  • Epitopes
  • Histocompatibility Antigens Class II
  • Macrolides
  • Receptors, Antigen, T-Cell, alpha-beta
  • Nickel
  • concanamycin A
  • strontium chloride
  • Strontium