The role of calcium homeostasis and flux during bacterial antigen processing in murine macrophages.
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.
Delvig
A A
AA
Department of Immunology, The Medical School, Newcastle University, Newcastle upon Tyne, GB. delvig@ncl.ac.uk
Robinson
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006706:Homeostasis; D017136:Ion Transport; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D015220:Calcium Channels; D002352:Carrier Proteins; D002614:Chelating Agents; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C014689:streptococcal M protein; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium