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The syntaxin 11 (STX11) gene is mutated in a proportion of patients with familial haemophagocytic lymphohistiocytosis (FHL) and exocytosis of cytotoxic granules is impaired in STX11-deficient NK cells. However, the subcellular localization, regulation of expression and molecular function of STX11 in NK cells and other cytotoxic lymphocytes remain unknown. Here we demonstrate that STX11 expression is strictly controlled by several mechanisms in a cell-type-specific manner and that the enzymatic activity of the proteasome is required for STX11 expression in NK cells. In resting NKL cells, STX11 was localized in the cation-dependent mannose-6-phosphate receptor (CD-M6PR)-containing compartment, which was clearly distinct from cytotoxic granules or Rab27a-expressing vesicles. These subcellular structures appeared to fuse at the contact area with NK-sensitive target cells as demonstrated by partial colocalization of STX11 with perforin and Rab27a. Although STX11-deficent allo-specific cytotoxic T-lymphocytes efficiently lysed target cells and released cytotoxic granules, they exhibited a significantly lower extent of spontaneous association of perforin with Rab27a as compared with STX11-expressing T cells. Thus, our results suggest that STX11 promotes the fusion of Rab27a-expressing vesicles with cytotoxic granules and reveal an additional level of complexity in the spatial/temporal segregation of subcellular structures participating in the process of granule-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Focuses on the in vivo basis for murine cytomegalovirus (MCMV) resistance to killing by natural killer (NK) cells. Resistance against infections by NK cells; Dual function of MCMV.

Discusses a study that investigates the effect of major histocompatibility complex (MHC) receptors on natural killer (NK) cells. Function of MHC class I molecules in the immune system; expression of MHC; Description of an immunoglobulin-type receptor, KIR2DL2, which is the focus of the study; Difference between MHC receptors in mice and humans.

Examines the method by which natural killer (NK) cells recognize and eliminate target cells. Recognition of major histocompatibility complexes (MHC); Binding of a peptide to the empty human leukocyte antigen (HLA)-B27 class I molecules of normal cells; Effector inhibition model of NK cell operation; Target interference or masking model; Roles of peptides in NK recognition.