title: Acceleration of intracellular targeting of antigen by the B-cell antigen receptor: importance depends on the nature of the antigen-antibody interaction.
abstract: The B-cell antigen receptor (BCR) internalizes bound antigen such that antigen-derived peptides become associated with emigrating major histocompatibility complex (MHC) class II molecules for presentation to T cells. Experiments with B-cell transfectants reveal that BCR confers a specificity of intracellular targeting since chimeric antigen receptors which internalize antigen by virtue of a heterologous cytoplasmic domain do not necessarily give rise to presentation. In contrast, however, previous studies have shown that antigen binding to irrelevant cell surface molecules (e.g. transferrin receptor, MHC class I) can ultimately lead to presentation. The solution to this paradox appears to be that the intracellular targeting by BCR actually reflects an acceleration of antigen delivery. Depending on the nature of the BCR-antigen interaction, this accelerated targeting can be essential in determining whether or not internalization leads to significant presentation. Physiologically, the accelerated delivery of antigen by BCR could prove of particular importance early in the immune response when antigen-BCR interaction is likely to be poor.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: V R
authors.initials: VR
authors.lastname: Aluvihare
authors.forename: A A
authors.initials: AA
authors.lastname: Khamlichi
authors.forename: G T
authors.initials: GT
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: M S
authors.initials: MS
authors.lastname: Neuberger
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D008077:Lipoproteins, LDL / Q000235:genetics / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000235:genetics / Q000276:immunology; D009592:Nitrohydroxyiodophenylacetate / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000941:Antigens; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011947:Receptors, Antigen, B-Cell; D009592:Nitrohydroxyiodophenylacetate; D010047:Ovalbumin; D009113:Muramidase