Regulation of CD1 function and NK1.1 T cell selection and maturation by cathepsin S

Abstract

NK1.1+ T cells develop and function through interactions with cell surface CD1 complexes. In I-Ab 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, α-galactosylceramide (α-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-Ak, cathepsin S-/- mice do not accumulate class II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is cri..