Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo

被引:91
作者
Beers, C
Burich, A
Kleijmeer, MJ
Griffith, JM
Wong, P
Rudensky, AY [1 ]
机构
[1] Univ Washington, Howard Hughes Med Inst, Dept Immunol, Sch Med, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA
[3] Univ Utrecht, Med Ctr, Dept Cell Biol, Utrecht, Netherlands
关键词
D O I
10.4049/jimmunol.174.3.1205
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Epithelial cells at environmental interfaces provide protection from potentially harmful agents. including pathogens. In addition to serving as a physical barrier and producing soluble mediators of immunity, such as c1lokines; or antimicrobial peptidm- these cells are thought to function as nonprofessional APCs. In this regard, intestinal epithelial cells a re particularly prominent because. they express MHC class II molecules at the site of massive antigenic exposure. However, unlike bone marrow-derived professional APC, such as dendritic cells or B cells, little is known about the mechanisms of MHC class II presentation by the nonprofessional APC in vivo. The former use the lysosomal cysteine protease cathepsin S (Cat S), whereas thymic cortical epithelial cells use cathepsin L (Cat L) for invariant chain degradation and MHC class H maturation. Unexpectedly, we found that murine Cat S plays a critical role in invariant chain degradation in intestinal epithelial cells. Furthermore, we report that nonprofessional APC present a class H-bound endogenous peptide to naive CD4 T cells in vivo in a Cat S-dependent fashion. These results suggest that in vivo, both professional and nonprofessional MHC class II-expressing APC use Cat S, but not Cat L, for MHC class II-mediated Ag presentation.
引用
收藏
页码:1205 / 1212
页数:8
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