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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0803564v1 183/10/6069    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Kawahara, M. Articles by Rock, K. L. PubMed PubMed Citation Articles by Kawahara, M. Articles by Rock, K. L.

Analysis of the Role of Tripeptidyl Peptidase II in MHC Class I Antigen Presentation In Vivo¹

Masahiro Kawahara,^2* Ian A. York, Arron Hearn,^* Diego Farfan,^* and Kenneth L. Rock^3*

^*Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health (to K.L.R.). Core resources supported by the Diabetes Endocrinology Research Grant DK42520 were also used. M.K. was supported by Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad.

² Current address: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.

³ Address correspondence and reprint requests to Dr. Kenneth L. Rock, University of Massachusetts Medical School, Department of Pathology, Room S2-109, 55 Lake Avenue North, Worcester, MA 01655. E-mail address: Kenneth.Rock{at}umassmed.edu

⁴ Abbreviations used in this paper: ER, endoplasmic reticulum; DC, dendritic cell; KO, knockout; LCMV, lymphocytic choriomeningitis virus; MEF, mouse embryonic fibroblast; siRNA, small interfering RNA; TPPII, tripeptidyl peptidase II; WT, wild type.