Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responses.

作者: Charles F. Towne , Ian A. York , Levi B. Watkin , John S. Lazo , Kenneth L. Rock

DOI: 10.4049/JIMMUNOL.178.11.6923

关键词:

摘要: Long oligopeptides (>10 residues) are generated during the catabolism of cellular proteins in cytosol. To be presented to T cells, such peptides must trimmed by aminopeptidases proper size (typically 8–10 stably bind MHC class I molecules. Aminopeptidases also destroy epitopes trimming them even shorter lengths. Bleomycin hydrolase (BH) is a cytosolic aminopeptidase that has been suggested play key role generating I-presented peptides. We show BH-deficient cells from mice unimpaired their ability present N-extended precursors or whole Ags and express normal levels Similarly, develop CD8+ cell responses eight three different viruses vivo. Therefore, BH itself not essential for generation destruction In contrast, when BH−/− crossed lacking another aminopeptidase, leucine resulting BH−/−leucine aminopeptidase−/− progeny selective increase gp276 epitope lymphocytic choriomeningitis virus, whereas respond several other unchanged. does influence presentation some Ags, although its largely redundant with aminopeptidases.

参考文章(56)
Lars Stoltze, Markus Schirle, Gerold Schwarz, Christian Schröter, Michael W. Thompson, Louis B. Hersh, Hubert Kalbacher, Stefan Stevanovic, Hans-Georg Rammensee, Hansjörg Schild, Two new proteases in the MHC class I processing pathway Nature Immunology. ,vol. 1, pp. 413- 418 ,(2000) , 10.1038/80852
John S. Lazo, Eli Gorelik, Jitesh P. Jani, Jehangir S. Mistry, Said M. Sebti, Metabolic inactivation: a mechanism of human tumor resistance to bleomycin. Cancer Research. ,vol. 51, pp. 227- 232 ,(1991)
A Neisig, A J Sijts, J J Neefjes, F Ossendorp, M C Feltkamp, J Roelse, W M Kast, C J Melief, Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences. Journal of Immunology. ,vol. 154, pp. 1273- 1279 ,(1995)
Annie X. Y. Mo, Steven F. L. van Lelyveld, Abie Craiu, Kenneth L. Rock, Sequences That Flank Subdominant and Cryptic Epitopes Influence the Proteolytic Generation of MHC Class I-Presented Peptides Journal of Immunology. ,vol. 164, pp. 4003- 4010 ,(2000) , 10.4049/JIMMUNOL.164.8.4003
Kristen Lemerise, Paolo Cascio, Kenneth Rock, Alfred L. Goldberg, X. Y. Mo, Distinct Proteolytic Processes Generate the C and N Termini of MHC Class I-Binding Peptides Journal of Immunology. ,vol. 163, pp. 5851- 5859 ,(1999)
Charles F. Towne, Ian A. York, Joost Neijssen, Margaret L. Karow, Andrew J. Murphy, David M. Valenzuela, George D. Yancopoulos, Jacques J. Neefjes, Kenneth L. Rock, Leucine Aminopeptidase Is Not Essential for Trimming Peptides in the Cytosol or Generating Epitopes for MHC Class I Antigen Presentation Journal of Immunology. ,vol. 175, pp. 6605- 6614 ,(2005) , 10.4049/JIMMUNOL.175.10.6605
E. John Wherry, Tatiana N. Golovina, Susan E. Morrison, Gomathinayagam Sinnathamby, Michael J. McElhaugh, David C. Shockey, Laurence C. Eisenlohr, Re-evaluating the generation of a "proteasome-independent" MHC class I-restricted CD8 T cell epitope. Journal of Immunology. ,vol. 176, pp. 2249- 2261 ,(2006) , 10.4049/JIMMUNOL.176.4.2249
M Del Val, D López, Selective involvement of proteasomes and cysteine proteases in MHC class I antigen presentation. Journal of Immunology. ,vol. 159, pp. 5769- 5772 ,(1997)
Thomas Serwold, Stephanie Gaw, Nilabh Shastri, ER aminopeptidases generate a unique pool of peptides for MHC class I molecules Nature Immunology. ,vol. 2, pp. 644- 651 ,(2001) , 10.1038/89800