title: Modulation by epitope-specific antibodies of class II MHC-restricted presentation of the tetanus toxin antigen.
abstract: Above a certain affinity the dissociation rate of monovalent antigen from antibody becomes slower than the time taken for antigen capture, endocytosis and processing by professional antigen presenting cells. Thus, when high affinity antibodies drive antigen uptake, either directly via B-cell membrane immunoglobulin or indirectly via Fc receptors, the substrate for processing may frequently be an antigen/antibody complex. Here we review studies using the tetanus toxin antigen which show that bound antibodies can dramatically affect proteolytic processing, dependent on the epitope specificity and multiplicity of antibodies bound. Certain antibodies protect or 'footprint' specific domains of the antigen during processing in B-cell clones resulting in modulation of loading of class II MHC-restricted T-cell epitopes. Processing and class II MHC loading of some T-cell epitopes within the footprinted region was hindered, as might be expected, but, surprisingly, presentation of other T-cell epitopes was boosted considerably. These studies show that protein/protein complexes can be processed in an unpredictable fashion by antigen presenting cells and indicate a possible mechanism whereby cryptic T-cell epitopes might be revealed in autoimmune disease.
authors.affiliation: Department of Biochemistry, University of Dundee, UK. c.watts@dundee.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Watts
authors.forename: A
authors.initials: A
authors.lastname: Antoniou
authors.forename: B
authors.initials: B
authors.lastname: Manoury
authors.forename: E W
authors.initials: EW
authors.lastname: Hewitt
authors.forename: L M
authors.initials: LM
authors.lastname: Mckay
authors.forename: L
authors.initials: L
authors.lastname: Grayson
authors.forename: N F
authors.initials: NF
authors.lastname: Fairweather
authors.forename: P
authors.initials: P
authors.lastname: Emsley
authors.forename: N
authors.initials: N
authors.lastname: Isaacs
authors.forename: P D
authors.initials: PD
authors.lastname: Simitsek
mesh_terms: D000918:Antibody Specificity; D017951:Antigen Presentation; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D008285:Major Histocompatibility Complex; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology; D013744:Tetanus Toxin / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D013744:Tetanus Toxin