p46, a Novel Natural Killer Cell–specific Surface Molecule That Mediates Cell Activation
Simona Sivori,Massimo Vitale,Luigia Morelli,Lorenza Sanseverino,Raffaella Augugliaro,Cristina Bottino,Lorenzo Moretta,Alessandro Moretta +7 more
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TLDR
Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex–restricted cytolysis mediated by human NK cells.Abstract:
Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell–specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex–restricted cytolysis mediated by human NK cells.read more
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Journal ArticleDOI
Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis.
Alessandro Moretta,Cristina Bottino,Massimo Vitale,Daniela Pende,Claudia Cantoni,Maria Cristina Mingari,Roberto Biassoni,Lorenzo Moretta +7 more
TL;DR: The discovery of MHC-specific inhibitory receptors in mouse and in human clarified the molecular basis of this important NK cell function, and some of these receptors have now been identified in humans, thus shedding some light on the molecular mechanisms involved in NK cell activation during the process of natural cytotoxicity.
Journal ArticleDOI
Human natural killer cells
TL;DR: There has been a substantial gain in understanding of what and how NK-cells "see," lending important insights into their functions and purpose in normal immune surveillance.
Journal ArticleDOI
Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells.
Guido Ferlazzo,Ming L. Tsang,Lorenzo Moretta,Lorenzo Moretta,Giovanni Melioli,Ralph M. Steinman,Christian Münz +6 more
TL;DR: It is suggested that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.
Journal ArticleDOI
Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense.
Naoko Satoh-Takayama,Christian A. J. Vosshenrich,Christian A. J. Vosshenrich,Sarah Lesjean-Pottier,Sarah Lesjean-Pottier,Shinichiro Sawa,Matthias Lochner,Frederique Rattis,Jean-Jacques Mention,Jean-Jacques Mention,Kader Thiam,Nadine Cerf-Bensussan,Ofer Mandelboim,Gérard Eberl,James P. Di Santo,James P. Di Santo +15 more
TL;DR: RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces.
Journal ArticleDOI
Regulation of immune responses through inhibitory receptors.
TL;DR: The inhibitory-receptor superfamily appears to regulate many types of immune responses by blocking cellular activation signals.
References
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