Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo

M Kawahara, IA York, A Hearn, D Farfan… - The Journal of …, 2009 - journals.aai.org
M Kawahara, IA York, A Hearn, D Farfan, KL Rock
The Journal of Immunology, 2009journals.aai.org
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 …
Abstract
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.
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