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The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients

Markel, Gal, Mussaffi, Huda, Ling, Khoon-Lin, Salio, Mariolina, Gadola, Stephan, Steuer, Guy, Blau, Hannah, Achdout, Hagit, de Miguel, María, Gonen-Gross, Tsufit, Hanna, Jacob, Arnon, Tal I., Qimron, Udi, Volovitz, Ilan, Eisenbach, Lea, Blumberg, Richard S., Porgador, Angel, Cerundolo, Vincenzo and Mandelboim, Ofer (2004) The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients Blood, 103, (5), pp. 1770-1778. (doi:10.1182/blood-2003-06-2114). (PMID:14604968).

Record type: Article


The killing of natural killer (NK) cells is regulated by activating and inhibitory NK receptors that recognize mainly class I major histocompatibility complex (MHC) proteins. In transporter associated with antigen processing (TAP2)–deficient patients, killing of autologous cells by NK cells is therefore expected. However, none of the TAP2-deficient patients studied so far have suffered from immediate NK-mediated autoimmune manifestations. We have previously demonstrated the existence of a novel class I MHC–independent inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) interactions. Here, we identified 3 new siblings suffering from TAP2 deficiency. NK cells derived from these patients express unusually high levels of the various killer cell inhibitory receptors (KIRs) and the CEACAM1 protein. Importantly, the patients' NK cells use the CEACAM1 protein to inhibit the killing of tumor and autologous cells. Finally, we show that the function of the main NK lysis receptor, NKp46, is impaired in these patients. These results indicate that NK cells in TAP2-deficient patients have developed unique mechanisms to reduce NK killing activity and to compensate for the lack of class I MHC–mediated inhibition. These mechanisms prevent the attack of self-cells by the autologous NK cells and explain why TAP2-deficient patients do not suffer from autoimmune manifestations in early stages of life.

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Published date: 1 March 2004


Local EPrints ID: 175449
ISSN: 0006-4971
PURE UUID: 940f5cae-d09b-4322-bc2a-1fbe4ca74c6a

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Date deposited: 23 Feb 2011 15:01
Last modified: 18 Jul 2017 12:09

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Author: Gal Markel
Author: Huda Mussaffi
Author: Khoon-Lin Ling
Author: Mariolina Salio
Author: Stephan Gadola
Author: Guy Steuer
Author: Hannah Blau
Author: Hagit Achdout
Author: María de Miguel
Author: Tsufit Gonen-Gross
Author: Jacob Hanna
Author: Tal I. Arnon
Author: Udi Qimron
Author: Ilan Volovitz
Author: Lea Eisenbach
Author: Richard S. Blumberg
Author: Angel Porgador
Author: Vincenzo Cerundolo
Author: Ofer Mandelboim

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