Induction of heat-stable antigen expression by phagocytosis is involved in in vitro activation of unprimed CTL by macrophages.
Costimulation is required for activation of unprimed CTL. While the costimulatory molecules B7 and heat stable Ag (HSA) play a role in CTL response induction generated by dendritic cells, HSA but not B7 contributes to primary CTL response induced by macrophages (M phi), but only if particulate material has been ingested. This is a finding that correlates well with the observation that soon after phagocytosis of latex beads by M phi, cell surface expression of HSA rapidly increases. This increase could not be prevented by addition of drugs that blocked the synthesis or intracellular transport of newly synthesized HSA. However, inhibitors of protein kinase C did significantly down-regulate HSA expression. Other proteins appear to be regulated by a similar mechanism, because the surface expression of the CD45 isoform B220, of IL-2R, and of CD26 also increased immediately following ingestion of beads by M phi. These data suggest that there exists a sequestered pool of proteins that can be exposed coordinately at the cell surface via a protein kinase signaling mechanism that detects phagocytic events. In the case of HSA, we suggest that the ability to rapidly modulate the cell surface level of costimulatory molecules is a useful mechanism by which M phi are able to quickly up-regulate their T cell stimulatory capabilities during the time when, most likely, they are presenting foreign Ag.
De Bruijn
M L
ML
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Peterson
P A
PA
Jackson
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D006358:Hot Temperature; D016130:Immunophenotyping; D007840:Latex / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000954:Antigens, Surface; D007840:Latex; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase