No essential role for tripeptidyl peptidase II for the processing of LCMV-derived T cell epitopes.
The proteasome is critically involved in the production of MHC class I-restricted T cell epitopes. Approximately 20% of all peptides generated by the proteasome are too large for direct presentation by MHC class I molecules. Reits et al. (Immunity 2004. 20: 495-506) suggested that a major portion of proteasomal products are larger than 15 amino acids and require further degradation by the tripeptidyl peptidase II (TPPII) before becoming ligands of MHC class I molecules. Using the well-characterized lymphocytic choriomeningitis virus (LCMV) model, the role of TPPII in the processing of several LCMV-derived T cell epitopes was investigated. In contrast to Reits' proposal, TPPII inhibition and TPPII overexpression experiments revealed that five out of six LCMV-derived CD8(+) T cell epitopes were not affected by inhibition of TPPII, while one epitope (GP276) was slightly reduced upon TPPII overexpression. Additionally, we demonstrated that the processing of two epitopes derived from ovalbumin and murine cytomegalovirus were not altered by TPPII inhibition. We propose that TPPII is not generally required for the production of MHC class I peptides, but the presentation of some peptides can be negatively affected by TPPII.
Basler
Michael
M
Division of Immunology, Department of Biology, University of Constance, Konstanz, Germany. michael.basler@uni-konstanz.de
Groettrup
Marcus
M
D000626:Aminopeptidases; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D008024:Ligands; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009698:Nucleoproteins; D010446:Peptide Fragments; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases