title: Biological function of the soluble CEACAM1 protein and implications in TAP2-deficient patients.
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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.forename: Gil
authors.initials: G
authors.lastname: Katz
authors.forename: Khoon-Lin
authors.initials: KL
authors.lastname: Ling
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Raizy
authors.initials: R
authors.lastname: Gruda
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Sa'ar
authors.initials: S
authors.lastname: Mizrahi
authors.forename: Jacob
authors.initials: J
authors.lastname: Hanna
authors.forename: Tsufit
authors.initials: T
authors.lastname: Gonen-Gross
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Niva
authors.initials: N
authors.lastname: Lieberman
authors.forename: Noam
authors.initials: N
authors.lastname: Stren
authors.forename: Boaz
authors.initials: B
authors.lastname: Nachmias
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Guy
authors.initials: G
authors.lastname: Steuer
authors.forename: Hanna
authors.initials: H
authors.lastname: Blau
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Huda
authors.initials: H
authors.lastname: Mussaffi
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D015703:Antigens, CD / Q000097:blood / Q000502:physiology*; D000943:Antigens, Differentiation / Q000097:blood / Q000502:physiology*; D015815:Cell Adhesion Molecules; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008285:Major Histocompatibility Complex; D008297:Male; D045726:Metalloproteases / Q000502:physiology; D010375:Pedigree
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; C071692:TAP2 protein, human; D045726:Metalloproteases