Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses
Immunology & Virology Program
Department of Pathology
Medical Subject Headings
Aminopeptidases; Animals; Antigen Presentation; CD8-Positive T-Lymphocytes; Cells, Cultured; Cysteine Endopeptidases; *Cytotoxicity, Immunologic; Egg Proteins; Embryonic Stem Cells; Epitopes, T-Lymphocyte; Fibroblasts; Histocompatibility Antigens Class I; Immunodominant Epitopes; Leucyl Aminopeptidase; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Peptide Fragments; Viral Envelope Proteins
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
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Citation: J Immunol. 2007 Jun 1;178(11):6923-30.
Towne, Charles Fenton; York, Ian A.; Watkin, Levi B.; Lazo, John S.; and Rock, Kenneth L., "Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses" (2007). GSBS Student Publications. Paper 427.