title: Immunotherapeutic potential of the immunodominant T-cell epitope of lipocalin allergen Bos d 2 and its analogues.
abstract: Lipocalin allergens, which contain most of the important animal-derived respiratory sensitizers, induce T helper type 2 (Th2) deviation, but the reasons for this are not clear. To explore the prospects for peptide-based allergen immunotherapy and to elucidate the characteristics of the immunodominant epitope of Bos d 2, BALB/c mice were immunized with a peptide containing the epitope, peptides containing its analogues, peptides from the corresponding regions of other lipocalin proteins, and peptides with a homologous sequence. We observed that murine spleen cells recognized the immunodominant epitope of Bos d 2, p127-142, in almost the same way as human Bos d 2-specific T cells did. Enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) analyses showed that p127-142 and a corresponding peptide from horse Equ c 1 induced a Th2-deviated cellular response, whereas a homologous bacterial peptide from Spiroplasma citri induced a Th0-type response. Interestingly, the spleen cell response to the bacterial peptide and p127-142 was cross-reactive, that is, able to induce reciprocally the proliferation and cytokine production of primed spleen cells in vitro. More importantly, the peptides were able to skew the phenotype of T cells primed with the other peptide. Our results suggest that modified peptides can be useful in allergen immunotherapy.
authors.affiliation: Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland. Soili.Saarelainen@uku.fi
authors.forename: Soili A
authors.initials: SA
authors.lastname: Saarelainen
authors.forename: Tuure T
authors.initials: TT
authors.lastname: Kinnunen
authors.forename: Cécile
authors.initials: C
authors.lastname: Buhot
authors.forename: Ale T O
authors.initials: AT
authors.lastname: Närvänen
authors.forename: Anu K
authors.initials: AK
authors.lastname: Kauppinen
authors.forename: Marja A
authors.initials: MA
authors.lastname: Rytkönen-Nissinen
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
authors.forename: Tuomas I
authors.initials: TI
authors.lastname: Virtanen
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D052179:Antigens, Plant; D049109:Cell Proliferation; D002478:Cells, Cultured; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007114:Immunization / Q000379:methods; D016056:Immunodominant Epitopes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000276:immunology; D045642:Spiroplasma citri / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D000942:Antigens, Bacterial; D052179:Antigens, Plant; C113339:Bos d 2 allergen; D016207:Cytokines; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D015847:Interleukin-4; D007371:Interferon-gamma