Publikation
Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S
Wissenschaftlicher Artikel/Review - 01.12.2001
Riese R J, Locksley R, Ploegh H, Behar S M, Naumov Y, Chu C L, Lennon-Dumenil A M, Driessen Christoph, Stetson D, Villadangos J, Shi G P, Chapman H A
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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.