title: IgE sequences in individuals living in an area of endemic parasitism show little mutational evidence of antigen selection.
abstract: Patterns of somatic mutation in IgE genes from allergic individuals have been a focus of study for many years, but IgE sequences have never been reported from parasitized individuals. To study the role of antigen selection in the evolution of the anti-parasite response, we therefore generated 118 IgE sequences from donors living in Papua New Guinea (PNG), an area of endemic parasitism. For comparison, we also generated IgG1, IgG2, IgG3 and IgG4 sequences from these donors, as well as IgG1 sequences from Australian donors. IgE sequences had, on average, 23.0 mutations. PNG IgG sequences had average mutation levels that varied from 17.7 (IgG3) to 27.1 (IgG4). Mean mutation levels correlated significantly with the position of their genes in the constant region gene locus (IgG3 < IgG1 < IgG2 < IgG4). Interestingly, given the heavy, life-long antigen burden experienced by PNG villagers, average mutation levels in IgG sequences were little different to that seen in Australian IgG1 sequences (19.2). Patterns of mutation provide clear evidence of antigen selection in many IgG sequences. The percentage of IgG sequences that showed significant accumulations of replacement mutations in the complementarity determining regions ranged from 22% of IgG3 sequences to 39% of IgG2 sequences. By contrast, only 12% of IgE sequences had such evidence of antigen selection, and this was significantly less than in PNG IgG1, IgG2 and IgG4 subclass sequences (P < 0.01). The anti-parasite IgE response therefore has the reduced evidence of antigen selection that has previously been reported in studies of IgE sequences from allergic individuals.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: K J L
authors.initials: KJ
authors.lastname: Jackson
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: B A
authors.initials: BA
authors.lastname: Gaëta
authors.forename: P M
authors.initials: PM
authors.lastname: Siba
authors.forename: W
authors.initials: W
authors.lastname: Pomat
authors.forename: E
authors.initials: E
authors.lastname: Walpole
authors.forename: J
authors.initials: J
authors.lastname: Rimmer
authors.forename: W A
authors.initials: WA
authors.lastname: Sewell
authors.forename: A M
authors.initials: AM
authors.lastname: Collins
mesh_terms: D000328:Adult; D000818:Animals; D000940:Antigenic Variation / Q000235:genetics / Q000276:immunology; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D019295:Computational Biology / Q000379:methods; D006373:Helminthiasis / Q000276:immunology* / Q000469:parasitology; D006376:Helminths / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology; D010219:Papua New Guinea; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012424:Rural Population; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D000947:Antigens, Helminth; D022801:Complementarity Determining Regions; D007074:Immunoglobulin G; D007073:Immunoglobulin E