title: Immunotherapy with B cell epitopes ameliorates inflammatory responses in Balb/c mice.
abstract: Osmotin, a protein from the pathogenesis-related family (PR-5), has been identified as an allergen based on in-silico and in-vitro studies. In the present study, three B cell epitopes of osmotin with single and double amino acid modifications were studied for immunotherapy in a murine model. The single-modification peptides (P-1-1, P-2-1 and P-3-1) and double-modification peptides (P-1-2, P-2-2 and P-3-2) showed significantly lower immunoglobulin (Ig)E binding with patients' sera compared to osmotin (P < 0·01). These peptides showed reduced IgE binding compared to the unmodified peptides (B cell epitopes) P-1, P-2 and P-3. Among the modified peptides, P-2-1, P-3-1, P-2-2 and P-3-2 showed significant reduction in IgE binding and were used for immunotherapy in mice. The sera of mice group treated with peptides showed a significant increase in IgG2a level and a significant decrease in IgE and IgG1 levels (P < 0·05). The mice that received peptide immunotherapy showed a shift from a T helper type 2 (Th2) to Th1 type where interferon (IFN)-γ and interleukin (IL)-10 levels were elevated, with a significant increase in groups treated with peptides P-3-1 and P-3-2 (P < 0·05). There was a reduction in the IL-4 and IL-5 levels in bronchoalveolar lavage fluid (BALF) in the peptide-treated mice groups. Total cell count and eosinophil count in BALF of the peptide-treated groups was also reduced compared to the phosphate-buffered saline (PBS)-treated group. Lung histology showed a significant reduction in cellular infiltrate in mice treated with P-2-2 and P-3-2 compared to PBS. In conclusion, peptides P-2-2 and P-3-2 lowered inflammatory responses and induced a Th1 response in mice.
authors.affiliation: Allergy and Immunology Section, CSIR- Institute of Genomics and Integrative Biology, Delhi, India; Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: S N
authors.initials: SN
authors.lastname: Gaur
authors.forename: N
authors.initials: N
authors.lastname: Arora
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D010455:Peptides; D007073:Immunoglobulin E
keywords: epitopes; immunotherapy; mice; osmotin; peptides