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.