Abstract
Stimulation of CD4(+) helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-alpha/Ig-beta heterodimers which, second, target antigens to MHC class II-containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-alpha-associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-alpha cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide- MHC class II complexes through antigen targeting by BCR subunits.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation*
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Antigens, CD / chemistry
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Antigens, CD / physiology*
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Antigens, Viral / metabolism
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B-Lymphocytes / enzymology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Bacteriophage lambda / immunology
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CD79 Antigens
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Cytoplasm / immunology
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DNA-Binding Proteins*
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Enzyme Precursors / metabolism
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Enzyme Precursors / physiology*
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Epitopes, T-Lymphocyte / metabolism
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism*
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Intracellular Signaling Peptides and Proteins
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Lymphocyte Activation
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Lymphoma, B-Cell
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Mice
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Protein-Tyrosine Kinases / metabolism
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Protein-Tyrosine Kinases / physiology*
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Rats
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Receptors, Antigen, B-Cell / chemistry
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Receptors, Antigen, B-Cell / physiology*
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Repressor Proteins / immunology
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Syk Kinase
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Tumor Cells, Cultured
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Tyrosine / physiology
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Viral Proteins
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Viral Regulatory and Accessory Proteins
Substances
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Antigens, CD
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Antigens, Viral
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CD79 Antigens
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Cd79a protein, mouse
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DNA-Binding Proteins
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Enzyme Precursors
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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Intracellular Signaling Peptides and Proteins
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Receptors, Antigen, B-Cell
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Repressor Proteins
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Viral Proteins
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Viral Regulatory and Accessory Proteins
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phage repressor proteins
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Tyrosine
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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Syk protein, rat