Analysis of the Role of Tripeptidyl Peptidase II in MHC Class I Antigen Presentation In Vivo

作者：Kawahara Masahiro; York Ian A; Hearn Arron; Farfan Diego; Rock Kenneth L^*

来源：The Journal of Immunology, 2009, 183(10): 6069-6077.

DOI：10.4049/jimmunol.0803564

Previous experiments using enzyme inhibitors and RNA interference in cell lysates and cultured cells have suggested that tripeptidyl peptidase 11 (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, TPPH is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags in vivo. The Journal of Immunology, 2009, 183: 6069-6077.

• 出版日期2009-11-15