Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S.
NK1.1(+) T cells develop and function through interactions with cell surface CD1 complexes. In I-A(b) mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of the CD1-restricted antigen, alpha-galactosylceramide (alpha-GalCer). CD1 dysfunction is secondary to defective trafficking of CD1, which colocalizes with Ii fragments and accumulates within endocytic compartments of cathepsin S(-/-) DCs. I-A(k), cathepsin S(-/-) mice do not accumulate class II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is critically linked to processing of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.
Riese
R J
RJ
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Shi
G P
GP
Villadangos
J
J
Stetson
D
D
Driessen
C
C
Lennon-Dumenil
A M
AM
Chu
C L
CL
Naumov
Y
Y
Behar
S M
SM
Ploegh
H
H
Locksley
R
R
Chapman
H A
HA
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000502:physiology*; D018949:Antigens, CD1 / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D017637:Clonal Deletion / Q000502:physiology*; D003546:Cysteine Endopeptidases; D004187:Disaccharides / Q000276:immunology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport; D013047:Specific Pathogen-Free Organisms; D018089:Superantigens / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018949:Antigens, CD1; D000944:Antigens, Differentiation, B-Lymphocyte; D004187:Disaccharides; D005699:Galactosylceramides; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D018089:Superantigens; C045084:invariant chain; D015847:Interleukin-4; D007371:Interferon-gamma; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S