Abstract
We report that MHC class II (MHC-II)-restricted antigen processing of two CD4(+) T cell epitopes from the surface M protein of Streptococcus pyogenes in murine macrophages is dependent on intact calcium homeostasis and flux. We have previously shown that the CD4(+) T cell epitope 308-319 of the type 5 M protein is presented by newly synthesized MHC-II molecules via the classical pathway, while 17-31 is loaded on recycling MHC-II molecules via the recycling pathway. In this report we show that processing of viable bacteria for 308-319 presentation depended on the availability of intra- and extra cellular calcium, intact gadolinium-sensitive and/or T-type calcium channels, as well as on thapsigargin-sensitive homeostasis of intracellular calcium. In contrast, processing of 17-31 was independent of both intracellular calcium and gadolinium-sensitive calcium channels. The data suggest that alternative antigen processing pathways have different requirements for intracellular calcium homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antigen Presentation*
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Antigens, Bacterial / genetics
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Antigens, Bacterial / metabolism*
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Bacterial Outer Membrane Proteins*
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology
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CD4-Positive T-Lymphocytes / immunology
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Calcium / metabolism*
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Calcium Channels / metabolism
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Calcium Signaling
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Cell Line
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Chelating Agents / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Epitopes / genetics
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Epitopes / metabolism
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Histocompatibility Antigens Class II / metabolism
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Homeostasis
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Ion Transport
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / metabolism*
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Mice
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Molecular Sequence Data
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Streptococcus pyogenes / genetics
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Streptococcus pyogenes / immunology
Substances
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Antigens, Bacterial
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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Calcium Channels
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Carrier Proteins
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Chelating Agents
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Epitopes
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Histocompatibility Antigens Class II
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streptococcal M protein
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Egtazic Acid
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Calcium