Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha.
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.
Siemasko
Karyn
K
Department of Medicine, Section of Rheumatology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Skaggs
Brian J
BJ
Kabak
Shara
S
Williamson
Edward
E
Brown
Bruce K
BK
Song
Wenxia
W
Clark
Marcus R
MR
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
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