title: Differential immunogenicity and allergenicity of native and recombinant human lactoferrins: role of glycosylation.
abstract: Human native milk lactoferrin (LF) and recombinant forms of lactoferrin (rLF) are available with identical aa sequences, but different glycosylation patterns. Native lactoferrin (NLF) possesses the intrinsic ability to stimulate vigorous IgG and IgE antibody responses in BALB/c mice, whereas recombinant forms (Aspergillus or rice) are 40-fold less immunogenic and 200-fold less allergenic. Such differences are independent of endotoxin or iron content and the glycans do not contribute to epitope formation. A complex glycoprofile is observed for NLF, including sialic acid, fucose, mannose, and Lewis (Le)(x)  structures, whereas both rLF species display a simpler glycoprofile rich in mannose. Although Le(x)  type sugars play a Th2-type adjuvant role, endogenous expression of Le(x)  on NLF did not completely account for the more vigorous IgE responses it provoked. Furthermore, coadminstration of rLF downregulated IgE and upregulated IgG2a antibody responses provoked by NLF, but was without effect on responses to unrelated peanut and chicken egg allergens. These results suggest glycans on rLF impact the induction phase to selectively inhibit IgE responses and that differential glycosylation patterns may impact on antigen uptake, processing and/or presentation, and the balance between Th1 and Th2 responses.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. rachael.almond@manchester.ac.uk
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Almond
authors.forename: Brian F
authors.initials: BF
authors.lastname: Flanagan
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Antonopoulos
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001230:Aspergillus; D005260:Female; D006031:Glycosylation; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007781:Lactoferrin / Q000008:administration & dosage / Q000276:immunology*; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016269:Milk Hypersensitivity / Q000276:immunology*; D008894:Milk Proteins / Q000008:administration & dosage / Q000276:immunology*; D012275:Oryza; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: D007074:Immunoglobulin G; D008894:Milk Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D007781:Lactoferrin; D008358:Mannose