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* Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655;
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824; and
Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15260
Long oligopeptides (>10 residues) are generated during the catabolism of cellular proteins in the cytosol. To be presented to T cells, such peptides must be trimmed by aminopeptidases to the proper size (typically 8–10 residues) to stably bind to MHC class I molecules. Aminopeptidases also destroy epitopes by trimming them to even shorter lengths. Bleomycin hydrolase (BH) is a cytosolic aminopeptidase that has been suggested to play a key role in generating MHC class I-presented peptides. We show that BH-deficient cells from mice are unimpaired in their ability to present epitopes from N-extended precursors or whole Ags and express normal levels of MHC class I molecules. Similarly, BH-deficient mice develop normal CD8+ T cell responses to eight epitopes from three different viruses in vivo. Therefore, BH by itself is not essential for the generation or destruction of MHC class I peptides. In contrast, when BH–/– mice are crossed to mice lacking another cytosolic aminopeptidase, leucine aminopeptidase, the resulting BH–/–leucine aminopeptidase–/– progeny show a selective increase in CD8+ T cell responses to the gp276 epitope from lymphocytic choriomeningitis virus, whereas the ability to present and respond to several other epitopes is unchanged. Therefore, BH does influence presentation of some Ags, although its role is largely redundant with other aminopeptidases.
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 support by a National Institutes of Health grant (to K.L.R.) and by National Institutes of Health Training Grant AI07349 (to C.F.T.). Core resources supported by Diabetes Endocrinology Research Grant DK42520 were also used.
2 Address correspondence and reprint requests to Dr. Kenneth L. Rock, Department of Pathology, University of Massachusetts Medical Center, Room S2-109, 55 Lake Avenue North, Worcester, MA 01655-0125. E-mail address: Kenneth.Rock{at}umassmed.edu
3 Abbreviations used in this paper: ER, endoplasmic reticulum; ERAP1, ER aminopeptidase 1; LAP, leucine aminopeptidase; BH, bleomycin hydrolase; VSV, vesicular stomatitis virus; NP, nucleoprotein; MEF, mouse embryonic fibroblast; LCMV, lymphocytic choriomeningitis virus.
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