title: Ubiquitin-dependent control of class II MHC localization is dispensable for antigen presentation and antibody production.
abstract: Controlled localization of class II MHC molecules is essential for proper class II MHC-restricted antigen presentation and the subsequent initiation of an adaptive immune response. Ubiquitination of class II MHC molecules on cytosolic lysine (K225) of the β-chain has been shown to affect localization of the complex. We generated mice in which the endogenous β-chain locus is replaced with a GFP tagged mutant version that lacks the cytosolic lysine residue (I-A-β-K225R-EGFP). These mice have elevated levels of class II MHC as compared to I-A-β-EGFP mice, and immature bone marrow-derived dendritic cells show redistribution of class II MHC to the cell surface. Nonetheless, in these same cells efficiency of antigen presentation is unaffected in I-A-β-K225R-EGFP mice, as assayed for presentation of ovalbumin to appropriately specific T cells. The I-A-β-K225R-EGFP animals have normal CD4 T cell populations and are capable of generating antigen-specific antibody in response to model antigens and viral infection. We therefore conclude that in our experimental system modulation of trafficking by ubiquitination of residue K225 of the β-chain is not essential for the function of class II MHC products in antigen presentation or antibody production.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Annette M
authors.initials: AM
authors.lastname: McGehee
authors.forename: Karin
authors.initials: K
authors.lastname: Strijbis
authors.forename: Eduardo
authors.initials: E
authors.lastname: Guillen
authors.forename: Thomas
authors.initials: T
authors.lastname: Eng
authors.forename: Oktay
authors.initials: O
authors.lastname: Kirak
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000096:biosynthesis*; D049452:Green Fluorescent Proteins / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D025801:Ubiquitin / Q000502:physiology*
chemical_list: D000941:Antigens; D000949:Histocompatibility Antigens Class II; D025801:Ubiquitin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins