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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing*
-
Amino Acid Motifs
-
Animals
-
Antigen Presentation*
-
Antigens, CD / chemistry
-
Antigens, CD / genetics
-
Antigens, CD / metabolism*
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / ultrastructure
-
CD79 Antigens
-
Carrier Proteins / physiology*
-
Cell Cycle Proteins*
-
Endocytosis
-
Endosomes / metabolism
-
GRB2 Adaptor Protein
-
Mice
-
Microscopy, Immunoelectron
-
Models, Immunological
-
Models, Molecular
-
Phosphoproteins / physiology*
-
Phosphorylation
-
Phosphotyrosine / physiology
-
Proteins / metabolism
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-vav
-
Receptors, Antigen, B-Cell / chemistry
-
Receptors, Antigen, B-Cell / genetics
-
Receptors, Antigen, B-Cell / metabolism*
-
Receptors, Antigen, B-Cell / physiology*
-
Recombinant Fusion Proteins / metabolism
-
Tumor Cells, Cultured
Substances
-
Adaptor Proteins, Signal Transducing
-
Antigens, CD
-
B cell linker protein
-
CD79 Antigens
-
Carrier Proteins
-
Cd79a protein, mouse
-
Cell Cycle Proteins
-
GRB2 Adaptor Protein
-
Grb2 protein, mouse
-
Phosphoproteins
-
Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-vav
-
Receptors, Antigen, B-Cell
-
Recombinant Fusion Proteins
-
Vav1 protein, mouse
-
Phosphotyrosine