title: Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha.
abstract: Ags that cross-link the B cell Ag receptor are preferentially and rapidly delivered to the MHC class II-enriched compartment for processing into peptides and subsequent loading onto MHC class II. Proper sorting of Ag/receptor complexes requires the recruitment of Syk to the phosphorylated immunoreceptor tyrosine-based activation motif tyrosines of the B cell Ag receptor constituent Igalpha. We postulated that the Igalpha nonimmunoreceptor tyrosine-based activation motif tyrosines, Y(176) and Y(204), contributed to receptor trafficking. Igalpha(YDeltaF(176,204))/Igbeta receptors were targeted to late endosomes, but were excluded from the vesicle lumen and could not facilitate the presentation of Ag to T cells. Subsequent analysis demonstrated that phosphorylation of Y(176)/Y(204) recruited the B cell linker protein, Vav, and Grb2. Reconstitution of Igalpha(YDeltaF(176,204))/Igbeta with the B cell linker protein rescued both receptor-facilitated Ag presentation and entry into the MHC class II-enriched compartment. Thus, aggregation accelerates receptor trafficking by recruiting two separate signaling modules required for transit through sequential checkpoints.
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Karyn
authors.initials: K
authors.lastname: Siemasko
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Skaggs
authors.forename: Shara
authors.initials: S
authors.lastname: Kabak
authors.forename: Edward
authors.initials: E
authors.lastname: Williamson
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D051925:CD79 Antigens; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D051379:Mice; D016253:Microscopy, Immunoelectron; D018448:Models, Immunological; D008958:Models, Molecular; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C113939:B cell linker protein; D051925:CD79 Antigens; D002352:Carrier Proteins; C497882:Cd79a protein, mouse; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; C496619:Vav1 protein, mouse; D019000:Phosphotyrosine