MHC class I antigen processing of an Adenovirus CTL epitope is linked to the levels of immunoproteasomes in infected cells

被引:98
作者
Sijts, AJAM
Standera, S
Toes, REM
Ruppert, T
Beekman, NJCM
van Veelen, PA
Ossendorp, FA
Melief, CJM
Kloetzel, PM
机构
[1] Humboldt Univ, Med Sch Charite, Inst Biochem, D-10117 Berlin, Germany
[2] Leiden Univ, Med Ctr, Dept Immunohaematol, Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Blood Bank, Leiden, Netherlands
关键词
D O I
10.4049/jimmunol.164.9.4500
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Proteasomes are the major source for the generation of peptides bound by MHC class I molecules, To study the functional relevance of the IFN-gamma-inducible proteasome subunits low molecular mass protein 2 (LMP2), LMP7, and mouse embryonal cell (MEC) ligand 1 in Ag processing and concomitantly that of immunoproteasomes, we established the tetracycline-regulated mouse cell line MEC217, allowing the titrable formation of immunoproteasomes. Infection of MEC217 cells with Adenovirus type 5 (Ad5) and analysis of Ag presentation with Ad5-specific CTL showed that cells containing immunoproteasomes processed the viral early 1B protein (E1B)-derived epitope E1B(192-200) with increased efficiency, thus allowing a faster detection of viral entry in induced cells. Importantly, optimal CTL activation was already achieved at submaximal immunosubunit expression. In contrast, digestion of E1B-polypeptide with purified proteasomes in vitro yielded E1B(192-200) at quantities that were proportional to the relative contents of immunosubunits. Our data provide evidence that the IFN-gamma-inducible proteasome subunits, when present at relatively low levels as at initial stages of infection, already increase the efficiency of antigenic peptide generation and thereby enhance MHC class I Ag processing in infected cells.
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页码:4500 / 4506
页数:7
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