Functional expression and analysis of a human HLA-DQ restricted, nickel-reactive T cell receptor in mouse hybridoma cells.
Nickel-induced contact dermatitis represents a T cell mediated delayed type hyperreactivity. The elucidation of the molecular basis of T cell activation by Ni2+ ions may serve as a model for the understanding of other metal allergies. We describe here the expression of hybrid T cell antigen receptor (TCR) alpha- and beta-genes, containing rearranged human Ni-reactive variable and mouse constant regions, together with human CD4 in a mouse T cell hybridoma. The resulting hybridoma specifically responds to IL-2 secretion to Ni, but not to other metal ions in the presence of HLA-matched antigen-presenting cells. Loss of CD4 decreases, but does not completely abrogate this reactivity. The restricting HLA-DQ element is identified as consisting of DQA1*0101 and DQB1*0501; however, only some of the B cell lines homozygous for these molecules effectively present Ni to the hybridoma. We interpret these data to show that (i) Ni-reactivity is definitely mediated by alpha beta TCR variable regions; (ii) as for peptide-specific TCR, the CD4 co-receptor enhances Ni-reactivity, but is not absolutely essential; (iii) Ni2+ ions like nominal peptide antigens require HLA (here class II) molecules of the APC for presentation; (iv) the restricting molecule may require a special conformation or the association with a particular type of peptide or an as yet unidentified other surface structure on the antigen-presenting cell for effective Ni-presentation.
Vollmer
J
J
Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Weltzien
H U
HU
Dormoy
A
A
Pistoor
F
F
Moulon
C
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D000939:Epitopes; D006683:HLA-DQ Antigens / Q000502:physiology*; D006801:Humans; D006825:Hybridomas / Q000737:chemistry*; D008213:Lymphocyte Activation; D051379:Mice; D009532:Nickel / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D006683:HLA-DQ Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D009532:Nickel