Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S.
SourceImmunity, 15, 6, (2001), pp. 909--19
Article / Letter to editor
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SubjectHereditary and acquired vitreo-retinal disorders: experimental and clinical research and treatment.; Erfelijke en verworven vitreo-retinale aandoeningen: experimenteel en klinisch onderzoek en behandeling.
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.
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