Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo.
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 cytokines or antimicrobial peptides, these cells are thought to function as nonprofessional APCs. In this regard, intestinal epithelial cells are 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 II 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 II-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.
Beers
Courtney
C
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Burich
Andrew
A
Kleijmeer
Monique J
MJ
Griffith
Janice M
JM
Wong
Phillip
P
Rudensky
Alexander Y
AY
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003546:Cysteine Endopeptidases; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S