Biological function of the soluble CEACAM1 protein and implications in TAP2-deficient patients

Gal Markel, Hagit Achdout, Gil Katz, Khoon Lin Ling, Mariolina Salio, Raizy Gruda, Roi Gazit, Sa'ar Mizrahi, Jacob Hanna, Tsufit Gonen-Gross, Tal I. Arnon, Niva Lieberman, Noam Stren, Boaz Nachmias, Richard S. Blumberg, Guy Steuer, Hanna Blau, Vincenzo Cerundolo, Huda Mussaffi, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

Abstract

Interactions of natural killer (NK) cells with MHC class I proteins provide the main inhibitory signals controlling NK killing activity. It is therefore surprising to learn that TAP2-deficient patients suffer from autoimmune manifestations only occasionally in later stages of life. We have previously described that the CEACAM1-mediated inhibitory mechanism of NK cytotoxicity plays a major role in controlling NK autoreactivity in three newly identified TAP2-deficient siblings. This novel mechanism probably compensates for the lack of MHC class I-mediated inhibition. The CEACAM1 protein can also be present in a soluble form and the biological function of the soluble form of CEACAM1 with regard to NK cells has not been investigated. Here we show that the homophilic CEACAM1 interactions are abrogated in the presence of soluble CEACAM1 protein in a dose-dependent manner. Importantly, the amounts of soluble CEACAM1 protein detected in sera derived from the TAP2-deficient patients were dramatically reduced as compared to healthy controls. This dramatic reduction does not depend on the membrane-bound metalloproteinase activity. Thus, the expression of CEACAM1 and the absence of soluble CEACAM1 observed in the TAP2-deficient patients practically maximize the inhibitory effect and probably help to minimize autoimmunity in these patients.

Original languageEnglish
Pages (from-to)2138-2148
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number8
DOIs
StatePublished - Aug 2004

Keywords

  • CEACAM1
  • Human
  • MHC
  • NK cells
  • TAP2

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