title: Metal-protein complex-mediated transport and delivery of Ni2+ to TCR/MHC contact sites in nickel-specific human T cell activation.
abstract: Nickel allergy clearly involves the activation of HLA-restricted, skin-homing, Ni-specific T cells by professional APCs. Nevertheless, knowledge concerning the molecular details of metal-protein interactions underlying the transport and delivery of metal ions to APC during the early sensitization phase and their interactions with HLA and TCRs is still fragmentary. This study investigates the role of human serum albumin (HSA), a known shuttling molecule for Ni(2+) and an often-disregarded, major component of skin, in these processes. We show that Ni-saturated HSA complexes (HSA-Ni) induce and activate Ni-specific human T cells as potently as Ni salt solutions when present at equimolar concentrations classically used for in vitro T cell stimulation. However, neither HSA itself nor its Ni-binding N-terminal peptide are involved in determining the specificity of antigenic determinants. In fact, HSA could be replaced by xenogeneic albumins exhibiting sufficient affinity for Ni(2+) as determined by surface plasmon resonance (Biacore technology) or atomic absorption spectroscopy. Moreover, despite rapid internalization of HSA-Ni by APC, it was not processed into HLA-associated epitopes recognizable by Ni-specific T cells. In contrast, the presence of HSA-Ni in the vicinity of transient contacts between TCR and APC-exposed HLA molecules appeared to facilitate a specific transfer of Ni(2+) from HSA to high-affinity coordination sites created at the TCR/HLA-interface.
authors.affiliation: Max-Planck-Institut für Immunbiologie, Freiburg, Germany. thierse@immunbio.mpg.de
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Thierse
authors.forename: Corinne
authors.initials: C
authors.lastname: Moulon
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Allespach
authors.forename: Bastian
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Andrea
authors.initials: A
authors.lastname: Doetze
authors.forename: Stephan
authors.initials: S
authors.lastname: Kuppig
authors.forename: Doris
authors.initials: D
authors.lastname: Wild
authors.forename: Friedrich
authors.initials: F
authors.lastname: Herberg
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Weltzien
mesh_terms: D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015478:Antigens, Heterophile / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D001692:Biological Transport / Q000276:immunology; D002413:Cations, Divalent; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D005456:Fluorescent Dyes / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008667:Metalloproteins / Q000276:immunology; D009532:Nickel / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012709:Serum Albumin / Q000276:immunology / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015478:Antigens, Heterophile; D002413:Cations, Divalent; D005456:Fluorescent Dyes; D006680:HLA Antigens; D008667:Metalloproteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D012709:Serum Albumin; D006639:Histidine; D009532:Nickel