Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo.
Previous experiments using enzyme inhibitors and RNA interference in cell lysates and cultured cells have suggested that tripeptidyl peptidase II (TPPII) plays a role in creating and destroying MHC class I-presented peptides. However, its precise contribution to these processes has been controversial. To elucidate the importance of TPPII in MHC class I Ag presentation, we analyzed TPPII-deficient gene-trapped mice and cell lines from these animals. In these mice, the expression level of TPPII was reduced by >90% compared with wild-type mice. Thymocytes from TPPII gene-trapped mice displayed more MHC class I on the cell surface, suggesting that TPPII normally limits Ag presentation by destroying peptides overall. TPPII gene-trapped mice responded as well as did wild-type mice to four epitopes from lymphocytic choriomeningitis virus. The processing and presentation of peptide precursors with long N-terminal extensions in TPPII gene-trapped embryonic fibroblasts was modestly reduced, but in vivo immunization with recombinant lentiviral or vaccinia virus vectors revealed that such peptide precursors induced an equivalent CD8 T cell response in wild-type and TPPII-deficient mice. These data indicate that while TPPII contributes to the trimming of peptides with very long N-terminal extensions, TPPII is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags in vivo.
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Masahiro
M
Kawahara
Ian A
IA
York
Arron
A
Hearn
Diego
D
Farfan
Kenneth L
KL
Rock
D000626:Aminopeptidases / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D012697:Serine Endopeptidases / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection; D025801:Ubiquitin / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D012333:RNA, Messenger; D025801:Ubiquitin; D010047:Ovalbumin; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D011070:Poly I-C