title: Prediction of murine MHC class I epitopes in a major house dust mite allergen and induction of T1-type CD8+ T cell responses.
abstract: The group I (Der p 1) allergen of Dermatophagoides pteronyssinus (house dust mite, HDM) contains several T helper (Th) epitopes recognized by C57BL/6 mice, with the peptide (111-139) containing a dominant MHC class II-restricted epitope (113-127). Since CD8+ T cells are thought to play a role in the regulation of allergic disease, we examined the Der p 1 sequence for potential MHC class I-binding motifs and observed that residues 111-119 (FGISNYCQI) contain motifs for H-2Db and Kb. Furthermore, immunization of C57BL/6 mice with unadjuvanted Ty virus-like particles (VLP) carrying Der p 1 (111-139), a method known to induce murine cytotoxic T lymphocyte (CTL) responses, primed Der p 1 (111-119)-specific Db-restricted CTL which produce high levels of IFN-gamma and low levels of IL-5 and IL-6 in vitro (T1-type CTL). VLP carrying the minimal epitope (FGISNYCQI) also induced a CTL response following immunization without adjuvant by various routes. Der p 1 (111-139)-VLP adjuvanted with alum did not prime CTL in C57BL/6 mice but were found to prime Th1-type CD4+ T cells that recognize the overlapping peptide (113-127) and native protein. The ability to successfully predict allergen-specific CD8+ T cell epitopes and prime CD8+ and/or CD4+ T cell responses provides an opportunity to dissect the relative roles of these T cells in the regulation of allergic responses and may offer therapeutic potential for reprogramming Th2-type allergic responses.
authors.affiliation: British Biotech Pharmaceuticals Ltd, Oxford, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Harris
authors.forename: J F
authors.initials: JF
authors.lastname: Roth
authors.forename: N
authors.initials: N
authors.lastname: Savage
authors.forename: S A
authors.initials: SA
authors.lastname: Woodrow
authors.forename: I K
authors.initials: IK
authors.lastname: Hemingway
authors.forename: G F
authors.initials: GF
authors.lastname: Hoyne
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
authors.forename: G T
authors.initials: GT
authors.lastname: Layton
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D018956:CD5 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000145:classification / Q000276:immunology*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008925:Mites / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D018956:CD5 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D006023:Glycoproteins; D016056:Immunodominant Epitopes