title: Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.
abstract: Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. tokuray@hama-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: N
authors.initials: N
authors.lastname: Seo
authors.forename: M
authors.initials: M
authors.lastname: Fujie
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D017454:Dermatitis, Photoallergic / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007114:Immunization; D008239:Lysine; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015242:Ofloxacin / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D015363:Quinolones; D015242:Ofloxacin; D008239:Lysine