Differential presentation of the same MHC class I epitopes by fibroblasts and dendritic cells.
Ag is presented to CTL as peptide associated with MHC class I molecules, which are present on most types of cells. We have investigated the presentation of Db-restricted lymphocytic choriomeningitis virus (LCMV) peptides by a fibroblast line (MC57) and a dendritic cell line (JawsII) to splenocytes from LCMV-immune C57BL/6 mice. We found that when LCMV-infected MC57 were used to restimulate the spleen cells, the resulting CTL line lost its ability to respond to the two dominant epitopes of the immune response to LCMV glycoprotein (gp)33 and nucleoprotein (np)396 but remained strongly lytic for targets coated with the subdominant gp276 epitope. In contrast, when LCMV-infected JawsII cells were used to restimulate the splenocytes, the resulting line continued to target gp33 and np396 but lost reactivity to gp276. When uninfected JawsII or MC57 cells were coated with peptides and used as stimulators, the resulting CTL lines continued to recognize all three epitopes, indicating that costimulatory or other potential innate differences in Ag presentation between the two cell lines are unlikely to account for the selective expansion of CTL specificities. When infected, both cell types produce similar levels of infectious LCMV, have similar levels of the NP and GP proteins from which np396 and gp33 are derived, and can be recognized by CTL specific for each of the three epitopes. These data indicate that in the generation of peptides for MHC-I binding and presentation to CTL, MC57 and JawsII process the same set of virus proteins in quantitatively different ways.
Butz
E A
EA
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195, USA.
Bevan
M J
MJ
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000096:biosynthesis / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005354:Fibrosarcoma; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis
D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011506:Proteins; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases